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Historia, Ciencias, Saude--Manguinhos Dec 2015The pharmacist Theodoro Peckolt was one of the most important figures in the history of the chemistry of natural Brazilian products. Like other nineteenth-century...
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.
Topics: Animals; Antinematodal Agents; Brazil; Ficus; History, 19th Century; Hookworm Infections; Humans; Iron; Pharmacies; Pharmacists
PubMed: 26625923
DOI: 10.1590/S0104-59702015000400012 -
PLoS Neglected Tropical Diseases Sep 2015The implementation of soil-transmitted helminth (STH) treatment programmes occurs in varied environmental, social and economic contexts. Programme impact will be...
BACKGROUND
The implementation of soil-transmitted helminth (STH) treatment programmes occurs in varied environmental, social and economic contexts. Programme impact will be influenced by factors that affect the reduction in the prevalence and intensity of infections following treatment, as well as the subsequent rate of reinfection. To better understand the heterogeneity of programme impact and its underlying reasons, we investigated the influence of contextual factors on reduction in STH infection as part of the national school based deworming (SBD) programme in Kenya.
MATERIALS AND METHODS
Data on the prevalence and intensity of infection were collected within the monitoring and evaluation component of the SBD programme at baseline and after delivery of two annual treatment rounds in 153 schools in western Kenya. Using a framework that considers STH epidemiology and transmission dynamics, capacity to deliver treatment, operational feasibility and financial capacity, data were assembled at both school and district (county) levels. Geographic heterogeneity of programme impact was assessed by descriptive and spatial analyses. Factors associated with absolute reductions of Ascaris lumbricoides and hookworm infection prevalence and intensity were identified using mixed effects linear regression modelling adjusting for baseline infection levels.
PRINCIPAL FINDINGS
The reduction in prevalence and intensity of A. lumbricoides and hookworms varied significantly by county and within counties by school. Multivariable analysis of factors associated with programme impact showed that absolute A. lumbricoides reductions varied by environmental conditions and access to improved sanitation at schools or within the community. Larger reduction in prevalence and intensity of hookworms were found in schools located within areas with higher community level access to improved sanitation and within counties with higher economic and health service delivery indicator scores.
CONCLUSIONS
The study identifies factors associated with the impact of school-based deworming and in particular highlights how access to water, sanitation and hygiene and environmental conditions influence the impact of deworming programmes.
Topics: Ancylostomiasis; Animals; Antinematodal Agents; Ascariasis; Delivery of Health Care; Humans; Kenya; Neglected Diseases; Nematode Infections; Prevalence; Program Evaluation; Public Health; School Health Services; Socioeconomic Factors; Trichuriasis; Water
PubMed: 26421808
DOI: 10.1371/journal.pntd.0004108 -
Emerging Infectious Diseases Oct 2015
Topics: Adult; Ancylostoma; Ancylostomiasis; Animals; Communicable Diseases, Emerging; France; Hookworm Infections; Humans; Male; Myanmar; Zoonoses
PubMed: 26402483
DOI: 10.3201/eid2110.150695 -
Human Vaccines & Immunotherapeutics 2015Na-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...
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.
Topics: Adjuvants, Immunologic; Aluminum Hydroxide; Ancylostoma; Ancylostomiasis; Animals; Antibodies, Helminth; Antibodies, Neutralizing; Antigens, Helminth; Aspartic Acid Proteases; Drug Discovery; Female; Hookworm Infections; Mice, Inbred BALB C; Mutant Proteins; Plants, Genetically Modified; Quality Control; Recombinant Proteins; Nicotiana; Vaccines, Synthetic
PubMed: 26018444
DOI: 10.4161/21645515.2014.980199 -
Releve Epidemiologique Hebdomadaire Mar 2015
Topics: Adolescent; Albendazole; Ancylostoma; Ancylostomiasis; Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Child; Child, Preschool; Databases, Factual; Global Health; Humans; Infant; Mebendazole; Necator americanus; Necatoriasis; Primary Prevention; Soil; Trichuriasis; Trichuris
PubMed: 25745677
DOI: No ID Found -
Nature Genetics Apr 2015Hookworms infect over 400 million people, stunting and impoverishing them. Sequencing hookworm genomes and finding which genes they express during infection should help...
Hookworms infect over 400 million people, stunting and impoverishing them. Sequencing hookworm genomes and finding which genes they express during infection should help in devising new drugs or vaccines against hookworms. Unlike other hookworms, Ancylostoma ceylanicum infects both humans and other mammals, providing a laboratory model for hookworm disease. We determined an A. ceylanicum genome sequence of 313 Mb, with transcriptomic data throughout infection showing expression of 30,738 genes. Approximately 900 genes were upregulated during early infection in vivo, including ASPRs, a cryptic subfamily of activation-associated secreted proteins (ASPs). Genes downregulated during early infection included ion channels and G protein-coupled receptors; this downregulation was observed in both parasitic and free-living nematodes. Later, at the onset of heavy blood feeding, C-lectin genes were upregulated along with genes for secreted clade V proteins (SCVPs), encoding a previously undescribed protein family. These findings provide new drug and vaccine targets and should help elucidate hookworm pathogenesis.
Topics: Ancylostoma; Ancylostomatoidea; Ancylostomiasis; Animals; Base Sequence; Female; Genome, Helminth; Humans; Male; Molecular Sequence Data; Multigene Family; Phylogeny; Species Specificity; Transcriptome; Zoonoses
PubMed: 25730766
DOI: 10.1038/ng.3237 -
Historia, Ciencias, Saude--Manguinhos 2014Between 1916 and 1923, the Federal District and 11 Brazilian states entered into cooperation agreements with the International Health Board of the Rockefeller Foundation...
Between 1916 and 1923, the Federal District and 11 Brazilian states entered into cooperation agreements with the International Health Board of the Rockefeller Foundation to combat a rural endemic disease, namely ancylostomiasis. This paper presents the diary of Alan Gregg, one of the American physicians who worked in Brazil from 1919 to 1922. An interesting source to discuss issues relating to the history of public health in Brazil, in addition to information about the activities to combat ancylostomiasis developed by the Rockefeller Foundation in the country, the diary of the physician presents his impressions concerning nature, culture, politics and society in Brazil. In the diary excerpts presented here, however, aspects related to the professional activities performed by Gregg are prioritized.
Topics: Ancylostomiasis; Brazil; Disease Eradication; Foundations; History, 20th Century; Humans; International Cooperation; Medical Records; United States
PubMed: 25606735
DOI: 10.1590/S0104-59702014000400010 -
American Journal of Public Health Feb 2015
Topics: Ancylostoma; Ancylostomiasis; Anemia; Animals; History, 19th Century; History, 20th Century; Humans; Public Health; Puerto Rico
PubMed: 25521874
DOI: 10.2105/AJPH.2014.302225 -
Molecular and Biochemical Parasitology Nov 2014Nematodes are unable to synthesize fatty acids de novo and must acquire them from the environment or host. It is hypothesized that two unique classes of fatty acid and...
Nematodes are unable to synthesize fatty acids de novo and must acquire them from the environment or host. It is hypothesized that two unique classes of fatty acid and retinol binding proteins that nematodes produce (fatty acid and retinol binding (FAR) and nematode polyprotein antigen/allergen (NPA)) are used to meet this need. A partial cDNA has been cloned corresponding to four subunits of a putative Ancylostoma ceylanicum NPA (AceNPA). The translated amino acid sequence of AceNPA shares sequence identity with similar proteins from Dictyocaulus viviparus, Ascaris suum, and Ostertagia ostertagi. Immunoblot experiments using a polyclonal anti-AceNPA IgG revealed proteins corresponding to the expected sizes of single, as well as two or three un-cleaved NPA subunits in adult excretory/secretory proteins and soluble adult worm extracts. Immunohistochemistry experiments localize AceNPA to the cuticle, pseudocoelomic space and testes suggesting a role in hookworm biology that is distinct from what has previously been defined for other hookworm lipid binding proteins. A single recombinant subunit of AceNPA (rAceNPAb) demonstrated binding in vitro to fluorescent fatty acids DAUDA, cis-parinaric acid, as well as retinol, at equilibrium dissociation constants in the low micromolar range. Further, in vitro data reveal that rAceNPAb binds fatty acids with chain lengths of C12-C22, with the greatest affinities for arachidonic, linoleic (C18), and eicosapentaenoic (C20) acids.
Topics: Amino Acid Sequence; Ancylostoma; Ancylostomiasis; Animals; Antigens, Helminth; Cloning, Molecular; Cricetinae; DNA, Complementary; Fatty Acids; Female; Helminth Proteins; Humans; Male; Molecular Sequence Data; Sequence Alignment
PubMed: 25481749
DOI: 10.1016/j.molbiopara.2014.11.005 -
PLoS Neglected Tropical Diseases Sep 2014Hookworms infect millions of people worldwide and can cause severe clinical symptoms in their hosts. Prospective cohort studies in Brazil show high rates of hookworm...
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.
Topics: Ancylostoma; Ancylostomiasis; Animals; Blood Proteins; Cricetinae; Diet, Protein-Restricted; Disease Models, Animal; Female; Lipids; Protein Deficiency; Random Allocation
PubMed: 25254370
DOI: 10.1371/journal.pntd.0003184