DOCSLIB.ORG

Against Laboratory Models of Human Intestinal Nematode Infections

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Against Laboratory Models of Human Intestinal Nematode Infections In Vitro and In Vivo Efficacy of Monepantel (AAD 1566) against Laboratory Models of Human Intestinal Nematode Infections Lucienne Tritten1,2, Angelika Silbereisen1,2, Jennifer Keiser1,2* 1 Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland, 2 University of Basel, Basel, Switzerland Abstract Background: Few effective drugs are available for soil-transmitted helminthiases and drug resistance is of concern. In the present work, we tested the efficacy of the veterinary drug monepantel, a potential drug development candidate compared to standard drugs in vitro and in parasite-rodent models of relevance to human soil-transmitted helminthiases. Methodology: A motility assay was used to assess the efficacy of monepantel, albendazole, levamisole, and pyrantel pamoate in vitro on third-stage larvae (L3) and adult worms of Ancylostoma ceylanicum, Necator americanus and Trichuris muris. Ancylostoma ceylanicum-orN. americanus-infected hamsters, T. muris-orAscaris suum-infected mice, and Strongyloides ratti-infected rats were treated with single oral doses of monepantel or with one of the reference drugs. Principal Findings: Monepantel showed excellent activity on A. ceylanicum adults (IC50 = 1.7 mg/ml), a moderate effect on T. muris L3 (IC50 = 78.7 mg/ml), whereas no effect was observed on A. ceylanicum L3, T. muris adults, and both stages of N. americanus. Of the standard drugs, levamisole showed the highest potency in vitro (IC50 = 1.6 and 33.1 mg/ml on A. ceylanicum and T. muris L3, respectively). Complete elimination of worms was observed with monepantel (10 mg/kg) and albendazole (2.5 mg/kg) in A. ceylanicum-infected hamsters. In the N. americanus hamster model single 10 mg/kg oral doses of monepantel and albendazole resulted in worm burden reductions of 58.3% and 100%, respectively. Trichuris muris, S. ratti and A. suum were not affected by treatment with monepantel in vivo (following doses of 600 mg/kg, 32 mg/kg and 600 mg/kg, respectively). In contrast, worm burden reductions of 95.9% and 76.6% were observed following treatment of T. muris- and A. suum infected mice with levamisole (200 mg/kg) and albendazole (600 mg/kg), respectively. Conclusions/Significance: Monepantel reveals low or no activities against N. americanus, T. muris, S. ratti and A. suum in vivo, hence does not qualify as drug development candidate for human soil-transmitted helminthiases. Citation: Tritten L, Silbereisen A, Keiser J (2011) In Vitro and In Vivo Efficacy of Monepantel (AAD 1566) against Laboratory Models of Human Intestinal Nematode Infections. PLoS Negl Trop Dis 5(12): e1457. doi:10.1371/journal.pntd.0001457 Editor: James S. McCarthy, Queensland Institute for Medical Research, Australia Received March 9, 2011; Accepted November 16, 2011; Published December 27, 2011 Copyright: ß 2011 Tritten et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Jennifer Keiser is grateful to the Swiss National Science Foundation for financial support (project no. PPOOA-114941) (http.www.snf.ch). The work on Necator was supported by the Institute of One World Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected] Introduction isole, and ivermectin), all of which have been registered for human use before or during the 1980’s [8,9]. No new anthelmintic drug The hookworm species Ancylostoma duodenale and Necator for human use has reached the market since then. Moreover, none americanus, the whipworm Trichuris trichiura, the threadworm of these drugs are efficacious using single doses on all STH species, Strongyloides stercoralis, and the roundworm Ascaris lumbricoides are with particularly low efficacy observed on T. trichiura [10]. Relying soil-transmitted helminths (STH) of great public health impor- on only a handful of drugs is a precarious situation, in the light of a tance. Cumulatively, these parasites affect more than one billion possible emergence of drug resistance [10]. people globally, particularly in developing regions of Asia, Africa, Since drug resistance to nematodes of veterinary importance is and Latin America [1,2]. If untreated, infections with STH are widely spread and increasing in frequency, most of the present for years and patients suffer from moderate to severe anthelmintic drug research and development efforts are motivated intestinal disturbances, anemia, nutrient loss and profound by veterinary needs [11]. For example, albendazole, mebendazole, physical and mental deficiencies [3,4]. and pyrantel pamoate were originally developed for livestock and Helminth control relies primarily on the regular administration pets [12]. of anthelmintics, typically carried out within the framework of Monepantel (AAD1566) belongs to a new class of veterinary school-based deworming programs, once or twice a year [5–7]. anthelmintics, the amino-acetonitrile derivatives. It has been Five drugs are currently available for the treatment of infections proposed that monepantel interferes with nematode-specific with STH (albendazole, mebendazole, pyrantel pamoate, levam- acetylcholine receptor subunits, leading to body wall muscle www.plosntds.org 1 December 2011 | Volume 5 | Issue 12 | e1457 Nematocidal Activity of Monepantel Author Summary For the in vivo studies, drugs were suspended in 7% (v/v) Tween 80% and 3% (v/v) ethanol or DMSO/PEG shortly before Soil-transmitted helminthiases affect more than one billion treatment. people among the most vulnerable populations in developing countries. Currently, control of these infections Animals and Parasites primarily relies on chemotherapy. Only five drugs are Three-week-old male Syrian Golden hamsters were purchased available, all of which have been in use for decades. None from Charles River (Sulzfeld, Germany). Four-week-old female of the drugs are efficacious using single doses against all NMRI mice and 3-week-old female C57Bl/6J mice were soil-transmitted helminths (STH) species and show low purchased from Harlan (Horst, The Netherlands). Three-week- efficacy observed against Trichuris trichiura. In addition, the old female Wistar rats were purchased from Harlan (Horst, The limited availability of current drug treatments poses a Netherlands). precarious situation should drug resistance occur. There- fore, there is great interest to develop novel drugs against All animals were kept in macrolon cages under environmental- infections with STH. Monepantel, which belongs to a new ly-controlled conditions (temperature: 25uC, humidity: 70%, class of veterinary anthelmintics, the amino-acetonitrile light/dark cycle 12 h/12 h) and had free access to water and derivatives, might be a potential drug candidate in rodent food (Rodent Blox from Eberle NAFAG, Gossau, humans. It has been extensively tested against livestock Switzerland). They were allowed to acclimatize in the animal nematodes, and was found highly efficacious and safe for facility of the Swiss Tropical and Public Health Institute (Swiss animals. Here we describe the in vitro and in vivo effect of TPH) for 1 week before infection. The current study was approved monepantel, on Ancylostoma ceylanicum, Necator amer- by the local veterinary agency based on Swiss cantonal and icanus, Trichuris muris, Strongyloides ratti, and Ascaris suum, national regulations (permission no. 2070). five parasite-rodent models of relevance to human STH. Since we observed that monepantel showed only high Parasites and Infections activity on one of the hookworm species and lacked Ancylostoma ceylanicum third-stage larvae (L3) were kindly activity on the other parasites tested we cannot recom- provided by Prof. J. M. Behnke (University of Nottingham). The mend the drug as a development candidate for human A. ceylanicum life cycle [23] had been maintained at the Swiss TPH soil-transmitted helminthiases. since June 2009 [17]. To maintain the life cycle, hamsters were treated orally 1 day before infection and then twice weekly with paralysis and subsequent death of worms. Due to its unique mode 3 mg/kg hydrocortisone (HydrocortoneH, MSD) or with 1 mg/l of action, the drug has proven efficacy against nematodes infecting dexamethasone (dexamethasone water-soluble, Sigma-Aldrich) in livestock which are resistant to current anthelmintic drugs [13]. the drinking water. They were orally infected with 150 A. Monepantel has been extensively tested on different nematode ceylanicum L3, which had been harvested less than 1 month before isolates. Administered at a single oral dose of 2.5 mg/kg, it was infection and had been assessed microscopically for viability. found to be safe, well-tolerated by ruminant hosts, and showed Animals assigned to in vivo studies were not treated with high cure rates on fourth stage larvae and adult worms of 15 hydrocortisone and were infected with 300 L3. nematode species [13–16]. Due to its high and broad nematocidal Infective N. americanus L3 were the gift of Prof. S. H. Xiao activity, monepantel was considered to be a candidate for a human (National Institute for Parasitic Diseases, Shanghai). Hamsters health directed program. were immunosuppressed with dexamethasone as described above The aim of the present
Load more

Recommended publications
  • The Functional Parasitic Worm Secretome: Mapping the Place of Onchocerca Volvulus Excretory Secretory Products
    pathogens Review The Functional Parasitic Worm Secretome: Mapping the Place of Onchocerca volvulus Excretory Secretory Products Luc Vanhamme 1,*, Jacob Souopgui 1 , Stephen Ghogomu 2 and Ferdinand Ngale Njume 1,2 1 Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM, Université Libre de Bruxelles, Rue des Professeurs Jeener et Brachet 12, 6041 Gosselies, Belgium; [email protected] (J.S.); [email protected] (F.N.N.) 2 Molecular and Cell Biology Laboratory, Biotechnology Unit, University of Buea, Buea P.O Box 63, Cameroon; [email protected] * Correspondence: [email protected] Received: 28 October 2020; Accepted: 18 November 2020; Published: 23 November 2020 Abstract: Nematodes constitute a very successful phylum, especially in terms of parasitism. Inside their mammalian hosts, parasitic nematodes mainly dwell in the digestive tract (geohelminths) or in the vascular system (filariae). One of their main characteristics is their long sojourn inside the body where they are accessible to the immune system. Several strategies are used by parasites in order to counteract the immune attacks. One of them is the expression of molecules interfering with the function of the immune system. Excretory-secretory products (ESPs) pertain to this category. This is, however, not their only biological function, as they seem also involved in other mechanisms such as pathogenicity or parasitic cycle (molting, for example). Wewill mainly focus on filariae ESPs with an emphasis on data available regarding Onchocerca volvulus, but we will also refer to a few relevant/illustrative examples related to other worm categories when necessary (geohelminth nematodes, trematodes or cestodes).
    [Show full text]
  • Mechanistic and Single-Dose in Vivo Therapeutic Studies of Cry5b Anthelmintic Action Against Hookworms
    Mechanistic and Single-Dose In Vivo Therapeutic Studies of Cry5B Anthelmintic Action against Hookworms Yan Hu1., Bin Zhan2*., Brian Keegan2, Ying Y. Yiu1, Melanie M. Miller1, Kathryn Jones2, Raffi V. Aroian1* 1 Section of Cell and Developmental Biology, University of California San Diego, La Jolla, California, United States of America, 2 Section of Tropical Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America Abstract Background: Hookworm infections are one of the most important parasitic infections of humans worldwide, considered by some second only to malaria in associated disease burden. Single-dose mass drug administration for soil-transmitted helminths, including hookworms, relies primarily on albendazole, which has variable efficacy. New and better hookworm therapies are urgently needed. Bacillus thuringiensis crystal protein Cry5B has potential as a novel anthelmintic and has been extensively studied in the roundworm Caenorhabditis elegans. Here, we ask whether single-dose Cry5B can provide therapy against a hookworm infection and whether C. elegans mechanism-of-action studies are relevant to hookworms. Methodology/Principal Findings: To test whether the C. elegans invertebrate-specific glycolipid receptor for Cry5B is relevant in hookworms, we fed Ancylostoma ceylanicum hookworm adults Cry5B with and without galactose, an inhibitor of Cry5B-C. elegans glycolipid interactions. As with C. elegans, galactose inhibits Cry5B toxicity in A. ceylanicum. Furthermore, p38 mitogen-activated protein kinase (MAPK), which controls one of the most important Cry5B signal transduction responses in C. elegans, is functionally operational in hookworms. A. ceylanicum hookworms treated with Cry5B up-regulate p38 MAPK and knock down of p38 MAPK activity in hookworms results in hypersensitivity of A.
    [Show full text]
  • First Report of Ancylostoma Ceylanicum in Wild Canids Q ⇑ Felicity A
    International Journal for Parasitology: Parasites and Wildlife 2 (2013) 173–177 Contents lists available at SciVerse ScienceDirect International Journal for Parasitology: Parasites and Wildlife journal homepage: www.elsevier.com/locate/ijppaw Brief Report First report of Ancylostoma ceylanicum in wild canids q ⇑ Felicity A. Smout a, R.C. Andrew Thompson b, Lee F. Skerratt a, a School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland 4811, Australia b School of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, Western Australia 6150, Australia article info abstract Article history: The parasitic nematode Ancylostoma ceylanicum is common in dogs, cats and humans throughout Asia, Received 19 February 2013 inhabiting the small intestine and possibly leading to iron-deficient anaemia in those infected. It has pre- Revised 23 April 2013 viously been discovered in domestic dogs in Australia and this is the first report of A. ceylanicum in wild Accepted 26 April 2013 canids. Wild dogs (dingoes and dingo hybrids) killed in council control operations (n = 26) and wild dog scats (n = 89) were collected from the Wet Tropics region around Cairns, Far North Queensland. All of the carcasses (100%) were infected with Ancylostoma caninum and three (11.5%) had dual infections with A. Keywords: ceylanicum. Scats, positively sequenced for hookworm, contained A. ceylanicum, A. caninum and Ancylos- Ancylostoma ceylanicum toma braziliense, with A. ceylanicum the dominant species in Mount Windsor National Park, with a prev- Dingo Canine alence of 100%, but decreasing to 68% and 30.8% in scats collected from northern and southern rural Hookworm suburbs of Cairns, respectively.
    [Show full text]
  • Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes
    molecules Article Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes Zeynep Mirza 1, Ernesto R. Soto 1 , Yan Hu 1,2, Thanh-Thanh Nguyen 1, David Koch 1, Raffi V. Aroian 1 and Gary R. Ostroff 1,* 1 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; [email protected] (Z.M.); [email protected] (E.R.S.); [email protected] (Y.H.); [email protected] (T.-T.N.); [email protected] (D.K.); raffi[email protected] (R.V.A.) 2 Department of Biology, Worcester State University, Worcester, MA 01602, USA * Correspondence: gary.ostroff@umassmed.edu; Tel.: 508-856-1930 Academic Editor: Vaclav Vetvicka Received: 2 June 2020; Accepted: 24 June 2020; Published: 27 June 2020 Abstract: Soil-transmitted nematodes (STN) infect 1–2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many instances of reduced activity. Terpenes are a class of compounds with anthelmintic activity. Thymol, a natural monoterpene phenol, was used to help eradicate hookworms in the U.S. South circa 1910. However, the use of terpenes as anthelmintics was discontinued because of adverse side effects associated with high doses and premature stomach absorption. Furthermore, the dose–response activity of specific terpenes against STNs has been understudied. Here we used hollow, porous yeast particles (YPs) to efficiently encapsulate (>95%) high levels of terpenes (52% w/w) and evaluated their anthelmintic activity on hookworms (Ancylostoma ceylanicum), a rodent parasite (Nippostrongylus brasiliensis), and whipworm (Trichuris muris). We identified YP–terpenes that were effective against all three parasites.
    [Show full text]
  • Opportunistic Mapping of Strongyloides Stercoralis and Hookworm in Dogs in Remote Australian Communities
    pathogens Article Opportunistic Mapping of Strongyloides stercoralis and Hookworm in Dogs in Remote Australian Communities Meruyert Beknazarova 1,*, Harriet Whiley 1 , Rebecca Traub 2 and Kirstin Ross 1 1 Faculty of Science and Engineering, Flinders University, Bedford Park, SA 5042, Australia; harriet.whiley@flinders.edu.au (H.W.); kirstin.ross@flinders.edu.au (K.R.) 2 Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Parkville, VIC 3052, Australia; [email protected] * Correspondence: meruyert.cooper@flinders.edu.au or [email protected] Received: 27 April 2020; Accepted: 19 May 2020; Published: 21 May 2020 Abstract: Both Strongyloides stercoralis and hookworms are common soil-transmitted helminths in remote Australian communities. In addition to infecting humans, S. stercoralis and some species of hookworms infect canids and therefore present both environmental and zoonotic sources of transmission to humans. Currently, there is limited information available on the prevalence of hookworms and S. stercoralis infections in dogs living in communities across the Northern Territory in Australia. In this study, 274 dog faecal samples and 11 faecal samples of unknown origin were collected from the environment and directly from animals across 27 remote communities in Northern and Central Australia. Samples were examined using real-time polymerase chain reaction (PCR) analysis for the presence of S. stercoralis and four hookworm species: Ancylostoma caninum, Ancylostoma ceylanicum, Ancylostoma braziliense and Uncinaria stenocephala. The prevalence of S. stercoralis in dogs was found to be 21.9% (60/274). A. caninum was the only hookworm detected in the dog samples, with a prevalence of 31.4% (86/274). This study provides an insight into the prevalence of S.
    [Show full text]
  • The Genome and Transcriptome of the Zoonotic Hookworm Ancylostoma Ceylanicum Identify Infection-Specific Gene Families
    LETTERS OPEN The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families Erich M Schwarz1, Yan Hu2,3, Igor Antoshechkin4, Melanie M Miller3, Paul W Sternberg4,5 & Raffi V Aroian2,3 Hookworms infect over 400 million people, stunting and closely related to the free-living Caenorhabditis elegans than is the impoverishing them1–3. Sequencing hookworm genomes and free-living Pristionchus pacificus (Fig. 2)12–15. Treatments effective finding which genes they express during infection should against A. ceylanicum might thus also prove useful against other help in devising new drugs or vaccines against hookworms4,5. strongylids, such as Haemonchus contortus, that infect farm ani- Unlike other hookworms, Ancylostoma ceylanicum infects mals and depress agricultural productivity16. Characterizing the both humans and other mammals, providing a laboratory genome and transcriptome of A. ceylanicum is a key step toward such model for hookworm disease6,7. We determined an comparative analysis. A. ceylanicum genome sequence of 313 Mb, with We assembled an initial A. ceylanicum genome sequence of 313 Mb transcriptomic data throughout infection showing expression and a scaffold N50 of 668 kb, estimated to cover ~95% of the genome, of 30,738 genes. Approximately 900 genes were upregulated with Illumina sequencing and RNA scaffolding17,18 (Supplementary during early infection in vivo, including ASPRs, a cryptic Tables 1–3). The genome size was comparable to those of Ancylostoma subfamily of activation-associated secreted proteins (ASPs)8. caninum (347 Mb)19 and H. contortus (320–370 Mb)20,21 but larger Genes downregulated during early infection included than those of N.
    [Show full text]
  • Diffuse Unilateral Subacute Neuroretinitis Caused by Ancylostoma Hookworm
    RESEARCH LETTERS Diffuse Unilateral Subacute has been described as successful, albeit primarily in cases where a worm cannot be visualized in the patient’s eye (5). Neuroretinitis Caused by Left untreated, DUSN can progress toward optic nerve at- Ancylostoma Hookworm rophy and permanent vision loss. In their larval form, hookworms infect their hosts by penetrating intact skin. The larvae circulate through the Sven Poppert, Martin Heideking, blood to the heart and then reach the lungs, before being Hansjürgen Agostini, Moritz Fritzenwanker, coughed up and swallowed, thus entering the gastrointes- Nicole Wüppenhorst, Birgit Muntau, tinal tract. In the intestines, the larvae develop into adult Philipp Henneke, Winfried Kern, Jürgen Krücken, worms and start to reproduce. This leads to the fecal shed- Bernd Junker, Markus Hufnagel ding of eggs into the environment. A. ceylanicum is a zoo- Author affiliations: University Medical Center, Hamburg- notic hookworm predominantly found in dogs and cats Eppendorf, Hamburg (S. Poppert); Justus-Liebig-University in Southeast Asia, India, and Australia (6). It is the only Giessen Institute for Medical Microbiology, Giessen, Germany animal hookworm species known to cause patent intestinal (S. Poppert, M. Fritzenwanker); Bernhard Nocht Institute for infections in humans (6). Tropical Medicine, Hamburg, Germany (S. Poppert, B. Muntau); We report on a 10-year-old boy born in Columbia who University Hospital Tübingen Children’s Hospital, Tübingen, had been living with his foster parents in Germany for the Germany (M. Heideking); University Medical Center Freiburg previous 6 years. He had acute loss of vision in his right Center of Pediatrics and Adolescent Medicine, Freiburg, Germany eye.
    [Show full text]
  • Parasitic Organisms Chart
    Parasitic organisms: Pathogen (P), Potential pathogen (PP), Non-pathogen (NP) Parasitic Organisms NEMATODESNematodes – roundworms – ROUNDWORMS Organism Description Epidemiology/Transmission Pathogenicity Symptoms Ancylostoma -Necator Hookworms Found in tropical and subtropical Necator can only be transmitted through penetration of the Some are asymptomatic, though a heavy burden is climates, as well as in areas where skin, whereas Ancylostoma can be transmitted through the associated with anemia, fever, diarrhea, nausea, Ancylostoma duodenale Soil-transmitted sanitation and hygiene are poor.1 skin and orally. vomiting, rash, and abdominal pain.2 nematodes Necator americanus Infection occurs when individuals come Necator attaches to the intestinal mucosa and feeds on host During the invasion stages, local skin irritation, elevated into contact with soil containing fecal mucosa and blood.2 ridges due to tunneling, and rash lesions are seen.3 matter of infected hosts.2 (P) Ancylostoma eggs pass from the host’s stool to soil. Larvae Ancylostoma and Necator are associated with iron can penetrate the skin, enter the lymphatics, and migrate to deficiency anemia.1,2 heart and lungs.3 Ascaris lumbricoides Soil-transmitted Common in Sub-Saharan Africa, South Ascaris eggs attach to the small intestinal mucosa. Larvae Most patients are asymptomatic or have only mild nematode America, Asia, and the Western Pacific. In migrate via the portal circulation into the pulmonary circuit, abdominal discomfort, nausea, dyspepsia, or loss of non-endemic areas, infection occurs in to the alveoli, causing a pneumonitis-like illness. They are appetite. Most common human immigrants and travelers. coughed up and enter back into the GI tract, causing worm infection obstructive symptoms.5 Complications include obstruction, appendicitis, right It is associated with poor personal upper quadrant pain, and biliary colic.4 (P) hygiene, crowding, poor sanitation, and places where human feces are used as Intestinal ascariasis can mimic intestinal obstruction, fertilizer.
    [Show full text]
  • Cognitive and Microbiome Impacts of Experimental Ancylostoma Ceylanicum Hookworm Infections in Hamsters
    University of Massachusetts Medical School eScholarship@UMMS Open Access Articles Open Access Publications by UMMS Authors 2019-05-27 Cognitive and Microbiome Impacts of Experimental Ancylostoma ceylanicum Hookworm Infections in Hamsters Samuel C. Pan University of California - San Diego Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/oapubs Part of the Digestive System Commons, Nervous System Commons, Parasitic Diseases Commons, Parasitology Commons, and the Psychological Phenomena and Processes Commons Repository Citation Pan SC, Ward DV, Yin Y, Hu Y, Mostafa EA, Clark RE, Aroian RV. (2019). Cognitive and Microbiome Impacts of Experimental Ancylostoma ceylanicum Hookworm Infections in Hamsters. Open Access Articles. https://doi.org/10.1038/s41598-019-44301-4. Retrieved from https://escholarship.umassmed.edu/ oapubs/3864 Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 License. This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Open Access Articles by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. www.nature.com/scientificreports OPEN Cognitive and Microbiome Impacts of Experimental Ancylostoma ceylanicum Hookworm Infections in Received: 21 December 2018 Accepted: 13 May 2019 Hamsters Published: xx xx xxxx Samuel C. Pan1, Doyle V. Ward2, Yunqiang Yin3, Yan Hu3,6, Mostafa A. Elfawal3, Robert E. Clark4,5 & Raf V. Aroian3 Hookworms are one of the most prevalent and important parasites, infecting ~500 million people worldwide. Hookworm disease is among the leading causes of iron-defciency anemia in the developing world and is associated with signifcant growth stunting and malnutrition.
    [Show full text]
  • 62 – Worms and More Worms Speaker: Edward Mitre, MD
    62 –Worms and More Worms Speaker: Edward Mitre, MD Disclosures of Financial Relationships with Relevant Commercial Interests • None Worms and More Worms Edward Mitre, MD Bethesda, MD What are helminths? What are helminths? The most complex and fascinating organisms that routinely infect people Pathogenic Helminths How helminths differ from other pathogens Eukaryotic, multicellular animals • Lifespan most live for years ----- phylum Platyhelminths ----- --Its own phylum!!-- TREMATODES CESTODES NEMATODES • Metazoans – eukaryotic, multicellular organisms (flukes) (tapeworms) (roundworms) • often have complex lifecycles • induce Th2 responses with eosinophilia and IgE • with few exceptions*, DO NOT MULTIPLY WITHIN HOST Fasciolopsis Taenia Ascaris (* Strongyloides, Paracapillaria, Hymenolepis) Images CDC DPDx ©2021 Infectious Disease Board Review, LLC 62 –Worms and More Worms Speaker: Edward Mitre, MD Major Helminth Pathogens World Prevalence TREMATODES CESTODES NEMATODES Blood flukes Intestinal tapeworms Intestinal Ascaris > 400 million Schistosoma mansoni Taenia solium Ascaris lumbricoides Taenia saginata Ancylostoma duodenale Schistosoma japonicum Necator americanus Schistosoma haematobium Diphyllobothrium latum Trichuris trichiura Trichuris > 200 million (Hymenolepis nana) Strongyloides stercoralis Liver flukes Enterobius vermicularis Hookworm > 200 million Fasciola hepatica Larval cysts Taenia solium Tissue Invasive Clonorchis sinensis Echinococcus granulosus Wuchereria bancrofti Brugia malayi Opisthorchis viverrini Echinococcus multilocularis
    [Show full text]
  • Larva Migrans Importance Larva Migrans Is a Group of Clinical Syndromes That Result from the Movement of Overview Parasite Larvae Through Host Tissues
    Larva Migrans Importance Larva migrans is a group of clinical syndromes that result from the movement of Overview parasite larvae through host tissues. The symptoms vary with the location and extent of the migration. Organisms may travel through the skin (cutaneous larva migrans) or internal organs (visceral larva migrans). Some larvae invade the eye (ocular larva migrans). Each form of the disease can be caused by a number of organisms. The Last Updated: December 2013 syndromes are loosely defined and the list of causative agents varies with the author. Cutaneous Larva Migrans Larval migration in the skin of the host causes cutaneous larva migrans. These infections are often acquired by skin contact with environmental sources of larvae, such as the soil. The larvae cause a pruritic, migrating dermatitis as they travel through the skin. Many of these infections are self-limiting. Animal hookworms are the most common cause of cutaneous larva migrans in humans. Ancylostoma braziliense is the most important species. Less often, cutaneous larva migrans is caused by A. caninum, A.,ceylanicum, A. tubaeforme, Uncinaria stenocephala or Bunostomum phlebotomum. In their usual hosts, the entry of hookworm larvae into the skin is followed by penetration of the dermis. In the dermis, the larvae enter via veins or lymphatic vessels, eventually reach the blood, and migrate through the lungs before reaching the intestines, where they mature into adults. In abnormal hosts such as humans, zoonotic hookworms can enter the epidermis, but most species cannot readily penetrate the dermis. Instead, these larvae remain trapped in the skin. and migrate for a time in the epidermis before dying.
    [Show full text]
  • Chemosensory Mechanisms of Host Seeking and Infectivity in Skin-Penetrating Nematodes
    Chemosensory mechanisms of host seeking and infectivity in skin-penetrating nematodes Spencer S. Ganga,b,1, Michelle L. Castellettob, Emily Yanga,b, Felicitas Ruizb, Taylor M. Browna,b,2, Astra S. Bryantb, Warwick N. Grantc, and Elissa A. Hallema,b,3 aMolecular Biology Institute, University of California, Los Angeles, CA 90095; bDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095; and cDepartment of Physiology, Anatomy, and Microbiology, La Trobe University, Bundoora 3086, Australia Edited by L. B. Vosshall, The Rockefeller University, New York, NY, and approved June 8, 2020 (received for review June 5, 2019) Approximately 800 million people worldwide are infected with pathways in directing iL3s toward hosts in the environment one or more species of skin-penetrating nematodes. These para- (20–22). After finding and entering a host, iL3s also rely on the sites persist in the environment as developmentally arrested third- presence of host cues to trigger activation and resume develop- stage infective larvae (iL3s) that navigate toward host-emitted ment (13, 14, 23–31). cues, contact host skin, and penetrate the skin. iL3s then reinitiate Host-emitted chemosensory cues are generally species specific development inside the host in response to sensory cues, a process and, thus, are likely to be important for the ability of iL3s to called activation. Here, we investigate how chemosensation drives distinguish hosts from nonhosts. However, the chemosensory host seeking and activation in skin-penetrating nematodes. We behaviors of mammalian-parasitic nematodes remain poorly show that the olfactory preferences of iL3s are categorically dif- understood. In particular, remarkably little is known about the ferent from those of free-living adults, which may restrict host chemosensory behaviors of hookworms, despite their worldwide seeking to iL3s.
    [Show full text]