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[PMID]: 26018444
[Au] Autor:Pearson MS; Jariwala AR; Abbenante G; Plieskatt J; Wilson D; Bottazzi ME; Hotez PJ; Keegan B; Bethony JM; Loukas A
[Ad] Address:a Centre for Biodiscovery and Molecular Development of Therapeutics; Australian Institute of Tropical Health and Medicine; James Cook University; Cairns , Queensland , Australia.
[Ti] Title:New tools for NTD vaccines: A case study of quality control assays for product development of the human hookworm vaccine Na-APR-1M74.
[So] Source:Hum Vaccin Immunother;11(5):1251-7, 2015.
[Is] ISSN:2164-554X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Na-APR-1(M74) is an aspartic protease that is rendered enzymatically inactive by site-directed mutagenesis and is a candidate antigen component in the Human Hookworm Vaccine. The mutant protease exerts vaccine efficacy by inducing antibodies that neutralize the enzymatic activity of wild type enzyme (Na-APR-1wt) in the gut of the hookworm, thereby depriving the worm of its ability to digest its blood meal. Previously, canines immunized with Na-APR-1(M74) and challenged with Ancylostoma caninum were partially protected against hookworm challenge infection, especially from the loss in hemoglobin observed in control canines and canine immunoglobulin (Ig) G raised against Na-APR-1 was shown to inhibit the enzymatic activity of Na-APR-1 wt in vitro, thereby providing proof of concept of Na-APR-1(M74) as a vaccine antigen. The mutated version, Na-APR-1(M74), was then expressed at the cGMP level using a Nicotiana benthamiana expression system (Fraunhofer, CMB, Delaware, MD), formulated with Alhydrogel®, and used to immunize mice in a dose-ranging study to explore the enzyme-neutralizing capacity of the resulting anti- Na-APR-1(M74) IgG. As little as 0.99 µg of recombinant Na-APR-1(M74) could induce anti Na-APR-1(M74) IgG in mice that were capable of inhibiting Na-APR-1w t-mediated digestion of a peptide substrate by 89%. In the absence of enzymatic activity of Na-APR-1(M74) as a surrogate marker of protein functionality, we developed an assay based on the binding of a quenched fluorescence-labeled inhibitor of aspartic proteases, BODIPY-FL pepstatin A (BDP). Binding of BDP in the active site of Na-APR-1 wt was demonstrated by inhibition of enzymatic activity, and competitive binding with unlabelled pepstatin A. BDP also bound to Na-APR-1(M74) which was assessed by fluorescence polarization, but with an ∼ 50-fold reduction in the dissociation constant. Taken together, these assays comprise a "toolbox" that could be useful for the analyses of Na-APR-1(M74) as it proceeds through the clinical development as part of the Human Hookworm Vaccine pipeline.
[Mh] MeSH terms primary: Ancylostoma/enzymology
Ancylostomiasis/prevention & control
Antigens, Helminth/immunology
Aspartic Acid Proteases/immunology
Hookworm Infections/prevention & control
Recombinant Proteins/immunology
[Mh] MeSH terms secundary: Adjuvants, Immunologic/administration & dosage
Aluminum Hydroxide/administration & dosage
Ancylostoma/immunology
Animals
Antibodies, Helminth/blood
Antibodies, Neutralizing/blood
Antigens, Helminth/genetics
Aspartic Acid Proteases/genetics
Drug Discovery/methods
Female
Mice, Inbred BALB C
Mutant Proteins/genetics
Mutant Proteins/immunology
Plants, Genetically Modified/genetics
Plants, Genetically Modified/metabolism
Quality Control
Recombinant Proteins/genetics
Tobacco/genetics
Tobacco/metabolism
Vaccines, Synthetic/administration & dosage
Vaccines, Synthetic/genetics
Vaccines, Synthetic/immunology
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Adjuvants, Immunologic); 0 (Antibodies, Helminth); 0 (Antibodies, Neutralizing); 0 (Antigens, Helminth); 0 (Mutant Proteins); 0 (Recombinant Proteins); 0 (Vaccines, Synthetic); 5QB0T2IUN0 (Aluminum Hydroxide); EC 3.4.- (Aspartic Acid Proteases)
[Em] Entry month:1602
[Cu] Class update date: 160527
[Lr] Last revision date:160527
[Js] Journal subset:IM
[Da] Date of entry for processing:150528
[St] Status:MEDLINE
[do] DOI:10.4161/21645515.2014.980199

  2 / 1087 MEDLINE  
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[PMID]: 26402483
[Au] Autor:Brunet J; Lemoine JP; Lefebvre N; Denis J; Pfaff AW; Abou-Bacar A; Traub RJ; Pesson B; Candolfi E
[Ti] Title:Bloody Diarrhea Associated with Hookworm Infection in Traveler Returning to France from Myanmar.
[So] Source:Emerg Infect Dis;21(10):1878-9, 2015 Oct.
[Is] ISSN:1080-6059
[Cp] Country of publication:United States
[La] Language:eng
[Mh] MeSH terms primary: Ancylostoma/genetics
Ancylostomiasis/epidemiology
Hookworm Infections/epidemiology
[Mh] MeSH terms secundary: Adult
Ancylostoma/parasitology
Animals
Communicable Diseases, Emerging/epidemiology
France/epidemiology
Hookworm Infections/pathology
Hookworm Infections/transmission
Humans
Male
Myanmar/epidemiology
Zoonoses/epidemiology
[Pt] Publication type:LETTER
[Em] Entry month:1605
[Cu] Class update date: 151007
[Lr] Last revision date:151007
[Js] Journal subset:IM
[Da] Date of entry for processing:150925
[St] Status:MEDLINE
[do] DOI:10.3201/eid2110.150695

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[PMID]: 25468029
[Au] Autor:Furtado LF; Bello AC; dos Santos HA; Carvalho MR; Rabelo ÉM
[Ti] Title:First identification of the F200Y SNP in the ß-tubulin gene linked to benzimidazole resistance in Ancylostoma caninum.
[So] Source:Vet Parasitol;206(3-4):313-6, 2014 Dec 15.
[Is] ISSN:1873-2550
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Single nucleotide polymorphisms (SNPs) in the ß-tubulin isotype 1 gene in codons 167, 198 and 200 have been associated with benzimidazole resistance in some nematodes, although no polymorphisms in this gene have been described in the hookworm Ancylostoma caninum to date. This study aimed to screen for SNPs in the ß-tubulin isotype 1 gene at codons 198 and 200 associated with benzimidazole resistance in A. caninum worms recovered from naturally infected dogs from two Brazilian states (Minas Gerais and Piauí). To perform this analysis, a molecular technique based on the amplification refractory mutation system (ARMS-PCR) was standardized. A total of 110 individual worms recovered from 9 dogs in Piauí and 124 individual worms recovered from 10 dogs in Minas Gerais were analyzed using this methodology. The presence of a SNP at position 200 was observed at a low frequency (0.8%), which was only detected in the worm population from Minas Gerais State. A total of 75 randomly selected samples were sequenced to validate this technique, and the presence of the SNP was confirmed. Furthermore, SNP at position 198 were evaluated by sequencing, and none were detected in this region. This is the first report of the presence of a SNP in the ß-tubulin isotype 1 gene associated with benzimidazole resistance in an A. caninum population.
[Mh] MeSH terms primary: Ancylostoma/genetics
Ancylostomiasis/parasitology
Anthelmintics/pharmacology
Benzimidazoles/pharmacology
Drug Resistance/genetics
Polymorphism, Single Nucleotide/genetics
Tubulin/genetics
[Mh] MeSH terms secundary: Ancylostoma/drug effects
Ancylostoma/isolation & purification
Animals
Female
Male
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Anthelmintics); 0 (Benzimidazoles); 0 (Tubulin); E24GX49LD8 (benzimidazole)
[Em] Entry month:1605
[Js] Journal subset:IM
[Da] Date of entry for processing:150305
[St] Status:MEDLINE

  4 / 1087 MEDLINE  
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[PMID]: 26930954
[Au] Autor:Lan QL; Liu Q
[Ti] Title:[Upper gastrointestinal bleeding induced by hookworm infection: one case report].
[So] Source:Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi;27(5):558-9, 2015 Oct.
[Is] ISSN:1005-6661
[Cp] Country of publication:China
[La] Language:chi
[Ab] Abstract:This paper reports a case of upper gastrointestinal bleeding induced by hookworm infection, which was misdiagnosed at the beginning, and analyzes the causes of misdiagnosis.
[Mh] MeSH terms primary: Ancylostomiasis/complications
Ancylostomiasis/diagnosis
Diagnostic Errors
Gastrointestinal Hemorrhage/etiology
[Mh] MeSH terms secundary: Adult
Ancylostoma/isolation & purification
Ancylostoma/physiology
Ancylostomiasis/parasitology
Animals
Female
Gastrointestinal Hemorrhage/therapy
Gastrointestinal Tract/blood supply
Gastrointestinal Tract/parasitology
Host-Parasite Interactions
Humans
[Pt] Publication type:CASE REPORTS; ENGLISH ABSTRACT; JOURNAL ARTICLE
[Em] Entry month:1604
[Js] Journal subset:IM
[Da] Date of entry for processing:160302
[St] Status:MEDLINE

  5 / 1087 MEDLINE  
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SciELO Brazil full text

[PMID]: 26625923
[Au] Autor:Silva FT; Dias MO; Pinto Ada C; Santos NP
[Ad] Address:Instituto de Química, Universidade Federal do Rio de Janeiro, , fabio.chemistry@gmail.com.
[Ti] Title:"Pós de doliarina e ferro": um dos remédios importantes da Farmácia Peckolt. ["Doliarina and iron powder": an important medicine at Peckolt Pharmacy].
[So] Source:Hist Cienc Saude Manguinhos;22(4):1427-39, 2015 Dec.
[Is] ISSN:1678-4758
[Cp] Country of publication:Brazil
[La] Language:por
[Ab] Abstract:The pharmacist Theodoro Peckolt was one of the most important figures in the history of the chemistry of natural Brazilian products. Like other nineteenth-century pharmacists in Brazil, he developed formulations and sold them at his pharmacy in Rio de Janeiro, and these enjoyed great prestige in the eyes both of the public and the medical community. The article discusses the relation between the illness originally called "opilação" (ancylostomiasis, or hookworm) and nineteenth-century treatment. It focuses especially on Peckolt Pharmacy's "Doliarina and iron powder," a formulation extracted from the Ficus gomelleira rubber plant. One of the article's goals is to use modern methods to analyze Ficus gomelleira and identify the chemical composition of the drug.
[Pt] Publication type:ENGLISH ABSTRACT; JOURNAL ARTICLE
[Em] Entry month:1512
[Js] Journal subset:QIS
[St] Status:In-Process

  6 / 1087 MEDLINE  
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[PMID]: 26795262
[Au] Autor:Wisniewski M; Jaros S; Baska P; Cappello M; Dlugosz E; Wedrychowicz H
[Ad] Address:Division of Parasitology and Parasitic Diseases, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, 02-0787 Warsaw, Ciszewskiego 8, Poland. Electronic address: marcin_wisniewski@sggw.pl....
[Ti] Title:Hamsters vaccinated with Ace-mep-7 DNA vaccine produced protective immunity against Ancylostoma ceylanicum infection.
[So] Source:Exp Parasitol;163:1-7, 2016 Apr.
[Is] ISSN:1090-2449
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Hookworms are intestinal nematodes that infect up to 740 million people, mostly in tropical and subtropical regions. Adult worms suck blood from damaged vessels in the gut mucosa, digesting hemoglobin using aspartic-, cysteine- and metalloproteases. Targeting aspartic hemoglobinases using drugs or vaccines is therefore a promising approach to ancylostomiasis control. Based on homology to metalloproteases from other hookworm species, we cloned the Ancylostoma ceylanicum metalloprotease 7 cDNA (Ace-mep-7). The corresponding Ace-MEP-7 protein has a predicted molecular mass of 98.8 kDa. The homology to metallopeptidases from other hookworm species and its predicted transmembrane region support the hypothesis that Ace-MEP-7 may be involved in hemoglobin digestion in the hookworm gastrointestinal tract, especially that our analyses show expression of Ace-mep-7 in the adult stage of the parasite. Immunization of Syrian golden hamsters with Ace-mep-7 cDNA resulted in 50% (p < 0.01) intestinal worm burden reduction. Additionally 78% (p < 0.05) egg count reduction in both sexes was observed. These results suggest that immunization with Ace-mep-7 may contribute to reduction in egg count released into the environment during the A. ceylanicum infection.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1603
[Js] Journal subset:IM
[St] Status:In-Data-Review

  7 / 1087 MEDLINE  
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[PMID]: 25683006
[Au] Autor:Ropars N; Tisseau L; Darrieux L; Safa G
[Ad] Address:Service de dermatologie, centre hospitalier de Saint-Brieuc, 10, rue Marcel-Proust, 22000 Saint-Brieuc, France....
[Ti] Title:Larva migrans cutanée ankylostomienne acquise en Bretagne: une zone d'endémie méconnue ? [Hookworm-related cutaneous larva migrans acquired in Brittany: a little-known endemic area?].
[So] Source:Ann Dermatol Venereol;142(4):285-6, 2015 Apr.
[Is] ISSN:0151-9638
[Cp] Country of publication:France
[La] Language:fre
[Mh] MeSH terms primary: Ancylostomiasis/diagnosis
Endemic Diseases
Larva Migrans/diagnosis
[Mh] MeSH terms secundary: Aged
Ancylostomiasis/epidemiology
Biopsy
Diagnosis, Differential
Eosinophilia/etiology
France/epidemiology
Humans
Humidity
Impetigo/diagnosis
Larva Migrans/epidemiology
Male
Soil/parasitology
[Pt] Publication type:CASE REPORTS; LETTER
[Nm] Name of substance:0 (Soil)
[Em] Entry month:1602
[Js] Journal subset:IM
[Da] Date of entry for processing:150406
[St] Status:MEDLINE

  8 / 1087 MEDLINE  
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[PMID]: 25911163
[Au] Autor:Marcus AD; Higgins DP; Gray R
[Ad] Address:Faculty of Veterinary Science, The University of Sydney, McMaster Bldg B14, Sydney, New South Wales, 2006, Australia.
[Ti] Title:Ivermectin treatment of free-ranging endangered Australian sea lion (Neophoca cinerea) pups: effect on hookworm and lice infection status, haematological parameters, growth, and survival.
[So] Source:Parasitol Res;114(7):2743-55, 2015 Jul.
[Is] ISSN:1432-1955
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:A placebo-controlled study was used to investigate the effectiveness of ivermectin to treat hookworm (Uncinaria sanguinis) and lice (Antarctophthirus microchir) infections in free-ranging Australian sea lion (Neophoca cinerea) pups and to test the hypotheses that these parasitic infections cause anaemia, systemic inflammatory responses, and reduced growth, and contribute towards decreased pup survival. Ivermectin was identified as an effective and safe anthelmintic in this species. Pups administered ivermectin had significantly higher erythrocyte counts and significantly lower eosinophil counts compared to controls at 1-2 months post-treatment, confirming that U. sanguinis and/or A. microchir are causatively associated with disease and demonstrating the positive effect of ivermectin treatment on clinical health parameters. Higher growth rates were not seen in ivermectin-treated pups and, unexpectedly, relatively older pups treated with ivermectin demonstrated significantly reduced growth rates when compared to matched saline-control pups. Differences in survival were not identified between treatment groups; however, this was attributed to the unexpectedly low mortality rate of recruited pups, likely due to the unintended recruitment bias towards pups >1-2 months of age for which mortality due to hookworm infection is less likely. This finding highlights the logistical and practical challenges associated with treating pups of this species shortly after birth at a remote colony. This study informs the assessment of the use of anthelmintics as a tool for the conservation management of free-ranging wildlife and outlines essential steps to further the development of strategies to ensure the effective conservation of the Australian sea lion and its parasitic fauna.
[Mh] MeSH terms primary: Ancylostomatoidea/drug effects
Ancylostomiasis/veterinary
Anoplura/drug effects
Antiparasitic Agents/administration & dosage
Hookworm Infections/veterinary
Ivermectin/administration & dosage
Sea Lions/parasitology
[Mh] MeSH terms secundary: Ancylostomatoidea/physiology
Ancylostomiasis/blood
Ancylostomiasis/drug therapy
Ancylostomiasis/parasitology
Animals
Antiparasitic Agents/adverse effects
Australia
Endangered Species
Hookworm Infections/blood
Hookworm Infections/drug therapy
Hookworm Infections/parasitology
Ivermectin/adverse effects
Sea Lions/growth & development
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Antiparasitic Agents); 70288-86-7 (Ivermectin)
[Em] Entry month:1602
[Js] Journal subset:IM
[Da] Date of entry for processing:150624
[St] Status:MEDLINE
[do] DOI:10.1007/s00436-015-4481-4

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[PMID]: 26434973
[Au] Autor:Chirapongsathorn S; Kamath PS
[Ad] Address:Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; Division of Gastroenterology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Royal Thai Army, Bangkok, Thailand.
[Ti] Title:Iron-Deficiency Anemia With an Itch.
[So] Source:Mayo Clin Proc;90(10):1458, 2015 Oct.
[Is] ISSN:1942-5546
[Cp] Country of publication:England
[La] Language:eng
[Mh] MeSH terms primary: Ancylostoma/isolation & purification
Ancylostomiasis
Anemia, Iron-Deficiency
Anthelmintics/therapeutic use
Iron Compounds/therapeutic use
Pruritus/etiology
[Mh] MeSH terms secundary: Adult
Ancylostomiasis/complications
Ancylostomiasis/diagnosis
Ancylostomiasis/parasitology
Ancylostomiasis/physiopathology
Ancylostomiasis/therapy
Anemia, Iron-Deficiency/diagnosis
Anemia, Iron-Deficiency/drug therapy
Anemia, Iron-Deficiency/etiology
Anemia, Iron-Deficiency/physiopathology
Animals
Female
Humans
Treatment Outcome
[Pt] Publication type:CASE REPORTS; JOURNAL ARTICLE
[Nm] Name of substance:0 (Anthelmintics); 0 (Iron Compounds)
[Em] Entry month:1601
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:151005
[St] Status:MEDLINE

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[PMID]: 25254370
[Au] Autor:Pacanaro CP; Dias SR; Serafim LR; Costa MP; Aguilar E; Paes PR; Alvarez-Leite JI; Rabelo EM
[Ad] Address:Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil....
[Ti] Title:Evaluation of biochemical, hematological and parasitological parameters of protein-deficient hamsters infected with Ancylostoma ceylanicum.
[So] Source:PLoS Negl Trop Dis;8(9):e3184, 2014 Sep.
[Is] ISSN:1935-2735
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: Hookworms infect millions of people worldwide and can cause severe clinical symptoms in their hosts. Prospective cohort studies in Brazil show high rates of hookworm reinfection in malnourished children compared to well-nourished children, despite previous treatment. Additionally, soil-transmitted helminth (STH) infections can worsen the nutritional status of affected populations. Therefore, this study aims to clarify the effects of host malnutrition during Ancylostoma ceylanicum infection and how this infection affects host physiological parameters using a hamster model. METHODOLOGY/PRINCIPAL FINDINGS: Hamsters were divided into four experimental groups: normal diet or low-protein diet (also referred to as "malnourished") and A. ceylanicum infection or no infection. More severe pathogenesis was observed in the infected malnourished group, as demonstrated by significant decreases in the hemoglobin concentration, erythrocyte number and packed-cell volume compared to the non-infected malnourished group. Greater numbers of adult parasites and eggs were observed in the malnourished group compared to the control group; however, the oviposition rate was lower in the malnourished group. In general, greater values of total lipids were observed in malnourished animals compared to control animals, including lipids excreted in the stool. CONCLUSIONS: In this work, we have demonstrated that animals fed an isocaloric low-protein diet presented more severe pathogenesis when infected with A. ceylanicum. The increased lipid concentration in the liver and blood is related to the conversion of the excess carbohydrate into fatty acids that increase the concentration of triglycerides in general. Triglycerides were excreted in the feces, indicating that infection associated with malnutrition caused a greater loss of these molecules for this group of animals and confirming the hypothesis that both nutrition and infection are responsible for the malabsorption syndrome. Taken together, the results found in this work confirm the hypothesis that the nutritional condition of the host greatly influences the course of the infection.
[Mh] MeSH terms primary: Ancylostoma
Ancylostomiasis/metabolism
Ancylostomiasis/parasitology
Protein Deficiency/metabolism
Protein Deficiency/parasitology
[Mh] MeSH terms secundary: Ancylostomiasis/blood
Animals
Blood Proteins/metabolism
Cricetinae
Diet, Protein-Restricted
Disease Models, Animal
Female
Lipids/blood
Protein Deficiency/blood
Random Allocation
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Blood Proteins); 0 (Lipids)
[Em] Entry month:1601
[Js] Journal subset:IM
[Da] Date of entry for processing:140926
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0003184


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