DOCSLIB.ORG

Thomas Nutman, MD (NIAID)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Thomas Nutman, MD (NIAID) Great Neglected Diseases Network • Started by the Rockefeller Foundation in 1977 • First and only director Kenneth Warren • Networks of 14 research units across the world (US, UK, Egypt, Australia, Israel, Sweden, Mexico, Brazil, Thailand) – Multidisciplinary – Emphasis on research - immunology, biochemistry, molecular biology, genetics – Disease focus – parasitic infections including malaria • Lasted only 8 years – But spawned the careers of a generation of parasite-oriented scientists The Millenium Development Goals 1. Eradicate extreme poverty and hunger 2. Achieve universal primary education 3. Promote gender equality and empower women 4. Reduce child mortality 5. Improve maternal health 6. Combat HIV/AIDS, malaria and other diseases 7. Ensure environmental sustainability 8. Develop a global partnership for 2000-2015 MDGs development From GNDs to Neglected Tropical Diseases (NTDs) • Attributed to and popularized by – Peter Hotez – David Molyneux – Alan Fenwick • Grew out of frustration from the use of the term “Other Diseases” in MDG #6 as it – created a two-tier system (HIV, malaria vs everything else) – made public advocacy for these “other diseases” impossible – left out these “other diseases” in most discussions on global health • NTD “marketing” has driven funding worldwide The Neglected Tropical Diseases (NTDs) • The most prevalent infections of poor people – Up to half of the 2.7 billion people who live on less than $2 per day • Non-emerging ancient conditions • Indigenous populations • Chronic disabling conditions – Growth delays – Blindness – Disfigurement – Stigma • Poverty promoting conditions – Child development and education – Pregnancy outcome – Productive capacity The 10 Leading Causes of Life-Years Lost to Disability and Premature Death Lower respiratory tract infections 91.4 HIV-AIDS 84.5 Unipolar depression 67.3 Diarrheal diseases 62.0 Ischemic heart diseases 58.6 Neglected tropical diseases 56.6 Cerebrovascular diseases 49.2 Malaria 46.5 Road traffic accidents 38.7 Tuberculosis 34.7 0 20 40 60 80 100 Disability-Adjusted Life-Years (millions) The Neglected Tropical Diseases Scabies Snakebites Mycetoma and other deep mycoses Loiaisis Common Human Helminth Infections Schistosoma mansoni Echinococcus, Taenia spp >200 million infected >100 million infected Cestodes Brugia malayi Ancylostoma duodenale Onchocerca volvulus Nector americanus Wuchereria bancrofti Trematodes 576 million infected 157 million infected Nematodes Strongyloides stercoralis Ascaris lumbricoides 50-100 million infected >1 billion infected Trichinella spiralis Trichuris trichiura >600 million infected Babu and Nutman, Clin Immunol, 2017 Filarial Infections of Humans Infection Disease Number Wolbachia infected Wuchereria bancrofti Lymphatic Filariasis 120 million Yes Brugia spp. Lymphatic Filariasis 10 million Yes Onchocerca volvulus Onchocerciasis 29 million Yes Loa loa Loiasis 13 million No Mansonella ozzardi Mansonellosis ? Yes Mansonella perstans Perstans Filariasis ~90 million Yes Mansonella streptocerca Streptocerciasis ? ? Collectively 2nd leading cause of disability worldwide (>1.2 million DALYs lost) Loiasis • Ogranism-Loa loa • Vector - Chrysops spp. (deerfly) • Microfilariae: Blood-borne • Adult worms: subcutaneous • Prevalence - 13 million • Geographic Distribution - West and Central Africa • Host range - Human Geographic distribution of Loa loa infection Lifecycle of Loa loa (EGG) L1 ADULT L4 L2 L3 Loiasis - Clinical Manifestations • Asymptomatic (subclinical) • Non-specific – urticaria, pruritus, myalgias • Calabar swellings • Eyeworm • Complications – Endomyocardial fibrosis, renal disease, encephalopathy, entrapment neuropathy Loiasis – Calabar Swellings •Episodic angioedema •Most common on extremities •Duration -1-4 days Loiasis - Eyeworm Clinical differences between endemic and non-endemic patients with loiasis Manifestation Expatriate Endemic (Benin) N=42 N=51 Calabar swelling 80% 16% Eyeworm 10% 16% Asymptomatic 16% 74% Nonspecific Urticaria/myalgia/artrhralgia 54% ??? Complications Hematuria/proteinuria 21% 22% Endomyocardial fibrosis 2% ??? . Klion, A.D., A. Massougbodji, B.C. Sadeler, E.A. Ottesen, and T.B. Nutman. 1991 J Infect Dis 163:1318-1325 Clinical differences between endemic and non-endemic patients with loiasis Manifestation Expatriate Endemic N=144 N=37 Calabar swelling* 80% 15% Eyeworm* 14% 62% Asymptomatic (MF+)* 22% 74% Nonspecific Urticaria* 19% 2% Myalgia/arthralgia 22% 11% Dermatitis 24% 16% Lymphadenopathy* 11% 2% Herrick JA et al.Clin Infect Dis. 2015 ;60:684-693. Complications associated with Loa loa infection Manifestation Expatriate Endemic N=144 N=37 Hematuria/proteinuria 21% 22% Endomyocardial fibrosis 0.4% 0% Neuropsychiatric 0.4% 0% Pulmonary 2% 3% Herrick JA et al.Clin Infect Dis. 2015 ;60:684-693. Eosinophilic endomyocardial fibrosis in a patient with loiasis H and E Anti-Eo-MBP Modulation of Immune Response to Filarial Infection as a Function of Time Anti-filarial Eosinophils Chemotherapy IgE IgG4 Antibody and Eosinophil Responses Eosinophil and Antibody Response to Response to Bystander Anti-filarial Parasite Antigens Antigens/Allergens/Vaccines Chemotherapy Anti-IL-10 in vitro Life Cycle of Lymphatic Filariae CD4+ T Cell Responses Cell T CD4+ (EGG) L1 Life Cycle of Lymphatic Filariae ADULT 0 6 months 6 months Decades L2 (EGG) L4 L1 Early Infection Chronic Infection ADULT L3 Life Cycle of Lymphatic Filariae + L4 L2 (EGG) L1 L3 ADULT L4 L2 L3 Immune Responses as a Function of Time in Human Helminth Infection Response to bystander antigen/vaccines/allergens IgE/IgG1 Th1 TNF-a Response to parasite antigen IFN-g IgE/IgG4 Th17 IL-17 to parasite antigen MACs AAMs IL-4 Monos DCs Response IL-5 Eos Th2 IL-13 ILCs IL-10 AAMs NKs Tregs IL-10 Baso/ IL-10 MC Tregs TGF-b IL-10 TGF-b TCM Teff InItiation and Development Patency establIshment of adult of InfectIon worms Decades 0 2 weeks Up to 6 months // // Parasite Host Uncontrolled response Modulated response Pro-inflammatory Tolerant/suppressed -10 Immune-mediated pathology IL Patent subclinical Lympahtic Filariasis Onchocerciasis infection Loiasis Loiasis: treatment • Diethylcarbamazine (DEC) – treatment of choice – mechanism of action unknown – macro- and microfilaricidal – associated with severe side effects in patients with high levels of circulating microfilariae • Ivermectin – microfilaricidal – also associated with severe side effects in patients with high microfilarial levels Loiasis: adjunct therapy • Corticosteroids – decrease rate of microfilarial clearance – reduce severity of post-treatment reactions – DO NOT prevent severe CNS complications of treatment in patients with high microfilarial loads • Apheresis – transient reduction of microfilarial load – ?decreased incidence of severe side effects Filarapheresis From 1990 - present Efficiency of filarapheresis • Numbers – 46 heavily microfilaremic patients – 68 procedures • Often on successive days • Issues – Must be done at midday Average reduction 67% Periodicity of various microfilariae in blood Wb Ll Di Wb var Pac The Loa loa Genome Ce III Ll Wb Bm Chromosome Genes mapped Extraordinary degree of synteny among the filariae Number to largest scaffolds Desjardins et al Nature Genetics 2013 Worm kinases that are targets of FDA-approved drugs hapla malayi pacifica spriralis Classification FPKM Approved drugs L. loa W. bancrofti B. A. suum P. C. elegans C.briggsae M. T. AGC/DMPK/ROCK 58.18 1 1 2 1 0 1 1 1 1 Fasudil ATYPICAL/PIKK/FRAP 2 1 3 1 2 1 1 1 2 Temsirolimus TK/ABL 18.87 1 1 1 1 1 1 1 1 1 Imatinib, Nilotinib, Dasatinib TK/EGFR 0.18 1 1 1 2 1 1 1 1 1 Gefitinib, Erlotinib, Lapatinib TK/SRC 40.86 1 1 1 1 1 1 1 1 1 Dasatinib TKL/RAF/RAF 27.55 1 1 2 1 1 1 1 1 1 Sonafenib Structural similarity between the filarial abl- like kinase and the human Bcr-abl oncogene Loa loa Abl-like kinase Human Bcr-Abl 100.0100 LoaLoaAbl loa protein NAN WuchereriaW.banc.Abl bancrofti protein 62.162.1A Brugiabmaabl malayi protein 100.0100 AscarisA.suum suum Abl 92.492.4 Homohuman sapiens abl protein TrichinellaTspiralis spiralis protein SchistosomaSmaAbl mansoniprotein 79.279.2 70 60 50 40 30 20 10 0 70 60 50 40 30 20 10 0 AminoAmino Acid Acid Substitution Substitution per 100100 Residues residues Bootstrap(Bootstrap Trials Trials = =1000, 1000, Seed seed = 111) = 111 Repurposing imatinib for antifilarial chemotherapy L3 killing by imatinib Imatinib 0µM 100 100uM 80 50uM l a 25uM v i 60 v 10uM r u 5uM 40 S 0uM % 20 0 0 1 2 3 4 Days of exposure to imatinib Mf killing by imatinib 100 100uM 80 50uM l a 25uM v i 60 v 10uM r u 5uM 40 S 0uM % 20 0 Imatinib 50µM 0 1 2 3 4 Days of exposure to imatinib O’Connell EM et al, JID 2015 Filarial c-abl Localizes Most Strongly to the Female Reproductive Tract of the Filariae DAPI SHG Anti-cABL Merge Fertilized ova Fertilized Morula stage Morula Pretzel stage Pretzel Isotype control O’Connell EM, et al. PLoS NTD, 2017 Clinical Protocol to Establish Efficacy and Safety of Single Dose Imatinib in Loa loa Microfilaremia Randomized-controlled dose escalation trial of imatinib, evaluating the kinetics of Loa loa microfilarial (MF) response over 1 year in Cameroon Severe adverse reactions (encephalopathy, death) to ivermectin is related to the Loa loa MF count and the rapidity with which it works 60000 >20000 MF/mL 40000 Danger zone Ivermectin Desired Drug Microfilariae 20000 0 0 2 4 6 8 Days Proposed use: Give drug for routine mass Drug given drug administration (MDA) during MF nadir to avoid severe reactions. It Takes a Village Large Community.
Load more

Recommended publications
  • Coinfection of Schistosoma (Trematoda) with Bacteria, Protozoa and Helminths
    CHAPTER 1 Coinfection of Schistosoma (Trematoda) with Bacteria, Protozoa and Helminths ,† ‡ Amy Abruzzi* and Bernard Fried Contents 1.1. Introduction 3 1.2. Coinfection of Species of Schistosoma and Plasmodium 4 1.2.1. Animal studies 21 1.2.2. Human studies 23 1.3. Coinfection of Schistosoma Species with Protozoans other than in the Genus Plasmodium 24 1.3.1. Leishmania 32 1.3.2. Toxoplasma 32 1.3.3. Entamoeba 34 1.3.4. Trypanosoma 35 1.4. Coinfection of Schistosoma Species with Salmonella 36 1.4.1. Animal studies 36 1.4.2. Human studies 42 1.5. Coinfection of Schistosoma Species with Bacteria other than Salmonella 43 1.5.1. Mycobacterium 43 1.5.2. Helicobacter pylori 49 1.5.3. Staphylococcus aureus 50 1.6. Coinfection of Schistosoma and Fasciola Species 50 1.6.1. Animal studies 57 1.6.2. Human studies 58 * Skillman Library, Lafayette College, Easton, Pennsylvania, USA { Epidemiology, University of Medicine and Dentistry of New Jersey (UMDNJ), Piscataway, New Jersey, USA { Department of Biology, Lafayette College, Easton, Pennsylvania, USA Advances in Parasitology, Volume 77 # 2011 Elsevier Ltd. ISSN 0065-308X, DOI: 10.1016/B978-0-12-391429-3.00005-8 All rights reserved. 1 2 Amy Abruzzi and Bernard Fried 1.7. Coinfection of Schistosoma Species and Helminths other than the Genus Fasciola 59 1.7.1. Echinostoma 59 1.7.2. Hookworm 70 1.7.3. Trichuris 70 1.7.4. Ascaris 71 1.7.5. Strongyloides and Trichostrongyloides 72 1.7.6. Filarids 73 1.8. Concluding Remarks 74 References 75 Abstract This review examines coinfection of selected species of Schisto- soma with bacteria, protozoa and helminths and focuses on the effects of the coinfection on the hosts.
    [Show full text]
  • Monophyly of Clade III Nematodes Is Not Supported by Phylogenetic Analysis of Complete Mitochondrial Genome Sequences
    UC Davis UC Davis Previously Published Works Title Monophyly of clade III nematodes is not supported by phylogenetic analysis of complete mitochondrial genome sequences Permalink https://escholarship.org/uc/item/7509r5vp Journal BMC Genomics, 12(1) ISSN 1471-2164 Authors Park, Joong-Ki Sultana, Tahera Lee, Sang-Hwa et al. Publication Date 2011-08-03 DOI http://dx.doi.org/10.1186/1471-2164-12-392 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Park et al. BMC Genomics 2011, 12:392 http://www.biomedcentral.com/1471-2164/12/392 RESEARCHARTICLE Open Access Monophyly of clade III nematodes is not supported by phylogenetic analysis of complete mitochondrial genome sequences Joong-Ki Park1*, Tahera Sultana2, Sang-Hwa Lee3, Seokha Kang4, Hyong Kyu Kim5, Gi-Sik Min2, Keeseon S Eom6 and Steven A Nadler7 Abstract Background: The orders Ascaridida, Oxyurida, and Spirurida represent major components of zooparasitic nematode diversity, including many species of veterinary and medical importance. Phylum-wide nematode phylogenetic hypotheses have mainly been based on nuclear rDNA sequences, but more recently complete mitochondrial (mtDNA) gene sequences have provided another source of molecular information to evaluate relationships. Although there is much agreement between nuclear rDNA and mtDNA phylogenies, relationships among certain major clades are different. In this study we report that mtDNA sequences do not support the monophyly of Ascaridida, Oxyurida and Spirurida (clade III) in contrast to results for nuclear rDNA. Results from mtDNA genomes show promise as an additional independently evolving genome for developing phylogenetic hypotheses for nematodes, although substantially increased taxon sampling is needed for enhanced comparative value with nuclear rDNA.
    [Show full text]
  • Pathophysiology and Gastrointestinal Impacts of Parasitic Helminths in Human Being
    Research and Reviews on Healthcare: Open Access Journal DOI: 10.32474/RRHOAJ.2020.06.000226 ISSN: 2637-6679 Research Article Pathophysiology and Gastrointestinal Impacts of Parasitic Helminths in Human Being Firew Admasu Hailu1*, Geremew Tafesse1 and Tsion Admasu Hailu2 1Dilla University, College of Natural and Computational Sciences, Department of Biology, Dilla, Ethiopia 2Addis Ababa Medical and Business College, Addis Ababa, Ethiopia *Corresponding author: Firew Admasu Hailu, Dilla University, College of Natural and Computational Sciences, Department of Biology, Dilla, Ethiopia Received: November 05, 2020 Published: November 20, 2020 Abstract Introduction: This study mainly focus on the major pathologic manifestations of human gastrointestinal impacts of parasitic worms. Background: Helminthes and protozoan are human parasites that can infect gastrointestinal tract of humans beings and reside in intestinal wall. Protozoans are one celled microscopic, able to multiply in humans, contributes to their survival, permits serious infections, use one of the four main modes of transmission (direct, fecal-oral, vector-borne, and predator-prey) and also helminthes are necked multicellular organisms, referred as intestinal worms even though not all helminthes reside in intestines. However, in their adult form, helminthes cannot multiply in humans and able to survive in mammalian host for many years due to their ability to manipulate immune response. Objectives: The objectives of this study is to assess the main pathophysiology and gastrointestinal impacts of parasitic worms in human being. Methods: Both primary and secondary data were collected using direct observation, books and articles, and also analyzed quantitativelyResults and and conclusion: qualitatively Parasites following are standard organisms scientific living temporarily methods. in or on other organisms called host like human and other animals.
    [Show full text]
  • Foodborne Anisakiasis and Allergy
    Foodborne anisakiasis and allergy Author Baird, Fiona J, Gasser, Robin B, Jabbar, Abdul, Lopata, Andreas L Published 2014 Journal Title Molecular and Cellular Probes Version Accepted Manuscript (AM) DOI https://doi.org/10.1016/j.mcp.2014.02.003 Copyright Statement © 2014 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial- NoDerivatives 4.0 International (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited. Downloaded from http://hdl.handle.net/10072/342860 Griffith Research Online https://research-repository.griffith.edu.au Foodborne anisakiasis and allergy Fiona J. Baird1, 2, 4, Robin B. Gasser2, Abdul Jabbar2 and Andreas L. Lopata1, 2, 4 * 1 School of Pharmacy and Molecular Sciences, James Cook University, Townsville, Queensland, Australia 4811 2 Centre of Biosecurity and Tropical Infectious Diseases, James Cook University, Townsville, Queensland, Australia 4811 3 Department of Veterinary Science, The University of Melbourne, Victoria, Australia 4 Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Townsville, Queensland, Australia 4811 * Correspondence. Tel. +61 7 4781 14563; Fax: +61 7 4781 6078 E-mail address: [email protected] 1 ABSTRACT Parasitic infections are not often associated with first world countries due to developed infrastructure, high hygiene standards and education. Hence when a patient presents with atypical gastroenteritis, bacterial and viral infection is often the presumptive diagnosis. Anisakid nematodes are important accidental pathogens to humans and are acquired from the consumption of live worms in undercooked or raw fish. Anisakiasis, the disease caused by Anisakis spp.
    [Show full text]
  • Diagnosis and Recommended Treatment of Helminth Infections
    DRUG REVIEW n Diagnosis and recommended treatment of helminth infections Allifia Abbas BSc, MRCP, Paul Wade MSc, BPharm and William Newsholme MSc, FRCP, DTM&H L P A number of worm infections are seen in the S UK, often in migrants from tropical coun - tries, and it is essential to take a travel his - tory. Our Drug review discusses the features of the most common infections and details currently recommended treatments. elminth infections (see Table 1) are major causes of mor - Hbidity in all age groups in the developing world. Around a quarter of the world population is infected with soil-transmit - ted helminths like hookworm and Ascaris , and nearly 250 mil - lion with schistosomiasis. In the developed world, due to improvements in hygiene and food safety, local transmission of infection is infrequent, though infections such as Enterobius remain common. However, with the increase in international travel, migration and more adventurous behav - iour, unusual helminth infections may be encountered any - where. Worldwide it is nematodes, or roundworms, that cause the bulk of infection. The soil-transmitted intestinal helminths Ascaris , hookworm, Trichuris and Strongyloides are good pop - ulation-level markers of poor hygiene and general deprivation, and cause growth and educational impairment in children and anaemia in pregnancy. Filaria are endemic in over 70 countries and infect about 120 million worldwide but are rare in travellers. Tissue helminths, such as Trichinella , may Figure 1. Adult hookworms can live in the small gut for years and can cause an become more frequent with increasing travel and dietary iron-deficiency anaemia in patient groups such as pregnant women adventure – the same is true for the lung and intestinal trema - todes, or flukes.
    [Show full text]
  • Mini-FLOTAC As an Alternative, Non-Invasive Diagnostic Tool For
    Catalano et al. Parasites Vectors (2019) 12:439 https://doi.org/10.1186/s13071-019-3613-6 Parasites & Vectors RESEARCH Open Access Mini-FLOTAC as an alternative, non-invasive diagnostic tool for Schistosoma mansoni and other trematode infections in wildlife reservoirs Stefano Catalano1,2* , Amelia Symeou1, Kirsty J. Marsh1, Anna Borlase1,2, Elsa Léger1,2, Cheikh B. Fall3, Mariama Sène4, Nicolas D. Diouf4, Davide Ianniello5, Giuseppe Cringoli5, Laura Rinaldi5, Khalilou Bâ6 and Joanne P. Webster1,2 Abstract Background: Schistosomiasis and food-borne trematodiases are not only of major public health concern, but can also have profound implications for livestock production and wildlife conservation. The zoonotic, multi-host nature of many digenean trematodes is a signifcant challenge for disease control programmes in endemic areas. However, our understanding of the epidemiological role that animal reservoirs, particularly wild hosts, may play in the transmission of zoonotic trematodiases sufers a dearth of information, with few, if any, standardised, reliable diagnostic tests avail- able. We combined qualitative and quantitative data derived from post-mortem examinations, coprological analyses using the Mini-FLOTAC technique, and molecular tools to assess parasite community composition and the validity of non-invasive methods to detect trematode infections in 89 wild Hubert’s multimammate mice (Mastomys huberti) from northern Senegal. Results: Parasites isolated at post-mortem examination were identifed as Plagiorchis sp., Anchitrema sp., Echinostoma caproni, Schistosoma mansoni, and a hybrid between Schistosoma haematobium and Schistosoma bovis. The reports of E. caproni and Anchitrema sp. represent the frst molecularly confrmed identifcations for these trematodes in defni- tive hosts of sub-Saharan Africa.
    [Show full text]
  • Parasites 1: Trematodes and Cestodes
    Learning Objectives • Be familiar with general prevalence of nematodes and life stages • Know most important soil-borne transmitted nematodes • Know basic attributes of intestinal nematodes and be able to distinguish these nematodes from each other and also from other Lecture 4: Emerging Parasitic types of nematodes • Understand life cycles of nematodes, noting similarities and significant differences Helminths part 2: Intestinal • Know infective stages, various hosts involved in a particular cycle • Be familiar with diagnostic criteria, epidemiology, pathogenicity, Nematodes &treatment • Identify locations in world where certain parasites exist Presented by Matt Tucker, M.S, MSPH • Note common drugs that are used to treat parasites • Describe factors of intestinal nematodes that can make them emerging [email protected] infectious diseases HSC4933 Emerging Infectious Diseases HSC4933. Emerging Infectious Diseases 2 Readings-Nematodes Monsters Inside Me • Ch. 11 (pp. 288-289, 289-90, 295 • Just for fun: • Baylisascariasis (Baylisascaris procyonis, raccoon zoonosis): Background: http://animal.discovery.com/invertebrates/monsters-inside-me/baylisascaris- [box 11.1], 298-99, 299-301, 304 raccoon-roundworm/ Video: http://animal.discovery.com/videos/monsters-inside-me-the-baylisascaris- [box 11.2]) parasite.html Strongyloidiasis (Strongyloides stercoralis, the threadworm): Background: http://animal.discovery.com/invertebrates/monsters-inside-me/strongyloides- • Ch. 14 (p. 365, 367 [table 14.1]) stercoralis-threadworm/ Videos: http://animal.discovery.com/videos/monsters-inside-me-the-threadworm.html http://animal.discovery.com/videos/monsters-inside-me-strongyloides-threadworm.html Angiostrongyliasis (Angiostrongylus cantonensis, the rat lungworm): Background: http://animal.discovery.com/invertebrates/monsters-inside- me/angiostrongyliasis-rat-lungworm/ Video: http://animal.discovery.com/videos/monsters-inside-me-the-rat-lungworm.html HSC4933.
    [Show full text]
  • Trichuriasis Importance Trichuriasis Is Caused by Various Species of Trichuris, Nematode Parasites Also Known As Whipworms
    Trichuriasis Importance Trichuriasis is caused by various species of Trichuris, nematode parasites also known as whipworms. Whipworms are common in the intestinal tracts of mammals, Trichocephaliasis, although their prevalence may be low in some host species or regions. Infections are Trichocephalosis, often asymptomatic; however, some individuals develop diarrhea, and more serious Whipworm Infestation effects, including dysentery, intestinal bleeding and anemia, are possible if the worm burden is high or the individual is particularly susceptible. T. trichiura is the species of whipworm normally found in humans. A few clinical cases have been attributed to Last Updated: January 2019 T. vulpis, a whipworm of canids, and T. suis, which normally infects pigs. While such zoonotic infections are generally thought uncommon, recent surveys found T. suis or T. vulpis eggs in a significant number of human fecal samples in some countries. T. suis is also being investigated in human clinical trials as a therapeutic agent for various autoimmune and allergic diseases. The rationale for its use is the correlation between an increased incidence of these conditions and reduced levels of exposure to parasites among people in developed countries. There is relatively little information about cross-species transmission of Trichuris spp. in animals. However, the eggs of T. trichiura have been detected in the feces of some pigs, dogs and cats in tropical areas with poor sanitation, raising the possibility of reverse zoonoses. One double-blind, placebo-controlled study investigated T. vulpis for therapeutic use in dogs with atopic dermatitis, but no significant effects were found. Etiology Trichuriasis is caused by members of the genus Trichuris, nematode parasites in the family Trichuridae.
    [Show full text]
  • Strongyloides Stercoralis
    Amor et al. Parasites & Vectors (2016) 9:617 DOI 10.1186/s13071-016-1912-8 RESEARCH Open Access High prevalence of Strongyloides stercoralis in school-aged children in a rural highland of north-western Ethiopia: the role of intensive diagnostic work-up Aranzazu Amor1,2*, Esperanza Rodriguez3, José M. Saugar3, Ana Arroyo4, Beatriz López-Quintana4, Bayeh Abera5, Mulat Yimer5, Endalew Yizengaw5, Derejew Zewdie5, Zimman Ayehubizu5, Tadesse Hailu5, Wondemagegn Mulu5, Adriana Echazú6,7, Alejandro J. Krolewieki6,7, Pilar Aparicio8, Zaida Herrador1, Melaku Anegagrie1,2 and Agustín Benito1 Abstract Background: Soil-transmitted helminthiases (hookworms, Ascaris lumbricoides and Trichuris trichiura) are extremely prevalent in school-aged children living in poor sanitary conditions. Recent epidemiological data suggest that Strongyloides stercoralis is highly unreported. However, accurate data are essential for conducting interventions aimed at introducing control and elimination programmes. Methods: We conducted a cross-sectional survey of 396 randomly selected school-aged children in Amhara region in rural area in north-western Ethiopia, to assess the prevalence of S. stercoralis and other intestinal helminths. We examined stools using three techniques: conventional stool concentration; and two S. stercoralis-specific methods, i.e. the Baermann technique and polymerase chain reaction. The diagnostic accuracy of these three methods was then compared. Results: There was an overall prevalence of helminths of 77.5%, with distribution differing according to school setting. Soil-transmitted helminths were recorded in 69.2%. Prevalence of S. stercoralis and hookworm infection was 20.7 and 54.5%, respectively, and co-infection was detected in 16.3% of cases. Schistosoma mansoni had a prevalence of 15.7%.
    [Show full text]
  • Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines
    Review Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines Donald P. McManus Molecular Parasitology Laboratory, Infectious Diseases Program, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia; [email protected]; Tel.: +61-(41)-8744006 Received: 24 August 2020; Accepted: 18 September 2020; Published: 22 September 2020 Abstract: Liver flukes (Fasciola spp., Opisthorchis spp., Clonorchis sinensis) and blood flukes (Schistosoma spp.) are parasitic helminths causing neglected tropical diseases that result in substantial morbidity afflicting millions globally. Affecting the world’s poorest people, fasciolosis, opisthorchiasis, clonorchiasis and schistosomiasis cause severe disability; hinder growth, productivity and cognitive development; and can end in death. Children are often disproportionately affected. F. hepatica and F. gigantica are also the most important trematode flukes parasitising ruminants and cause substantial economic losses annually. Mass drug administration (MDA) programs for the control of these liver and blood fluke infections are in place in a number of countries but treatment coverage is often low, re-infection rates are high and drug compliance and effectiveness can vary. Furthermore, the spectre of drug resistance is ever-present, so MDA is not effective or sustainable long term. Vaccination would provide an invaluable tool to achieve lasting control leading to elimination. This review summarises the status currently of vaccine development, identifies some of the major scientific targets for progression and briefly discusses future innovations that may provide effective protective immunity against these helminth parasites and the diseases they cause. Keywords: Fasciola; Opisthorchis; Clonorchis; Schistosoma; fasciolosis; opisthorchiasis; clonorchiasis; schistosomiasis; vaccine; vaccination 1. Introduction This article provides an overview of recent progress in the development of vaccines against digenetic trematodes which parasitise the liver (Fasciola hepatica, F.
    [Show full text]
  • Prevalence and Intensity of Infection of Soil-Transmitted Helminths in Latin America and the Caribbean Countries Mapping at Second Administrative Level 2000-2010
    2011 Prevalence and intensity of infection of Soil-transmitted Helminths in Latin America and the Caribbean Countries Mapping at second administrative level 2000-2010 0 March 18/2011 PAHO NTD Team Pan American Health Organization Communicable Disease Prevention and Control Project “Prevalence and intensity of infection of Soil-transmitted Helminths in Latin America and the Caribbean Countries: Mapping at second administrative level 2000-2010” Washington, D.C.: PAHO © 2011 1. Background 2. Objectives 3. Methodology 4. Outcomes 5. Discussion 6. Conclusions All rights reserved. This document may be reviewed, summarized, cited, reproduced, or translated freely, in part or in its entirety with credit given to the Pan American Health Organization. It cannot be sold or used for commercial purposes. The electronic version of this document can be downloaded from: www.paho.org. The ideas presented in this document are solely the responsibility of the authors. Requests for further information on this publication and other publications produced by Neglected and Parasitic Diseases Group, Communicable Disease Prevention and Control Project, HSD/CD should contact: Parasitic and Neglected Diseases Pan American Health Organization 525 Twenty-third Street, N.W. Washington, DC 20037-2895 www.paho.org. Recommended citation: Saboyá MI, Catalá L, Ault SK, Nicholls RS. Prevalence and intensity of infection of Soil-transmitted Helminths in Latin America and the Caribbean Countries: Mapping at second administrative level 2000-2010. Pan American Health Organization: Washington D.C., 2011. 1 March 18/2011 PAHO NTD Team Acknowledgments The Pan-American Health Organization (PAHO) would like to express special thanks to authors who contributed with copies of their papers directly, when free access was not available.
    [Show full text]
  • Praziquantel Treatment in Trematode and Cestode Infections: an Update
    Review Article Infection & http://dx.doi.org/10.3947/ic.2013.45.1.32 Infect Chemother 2013;45(1):32-43 Chemotherapy pISSN 2093-2340 · eISSN 2092-6448 Praziquantel Treatment in Trematode and Cestode Infections: An Update Jong-Yil Chai Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, Seoul, Korea Status and emerging issues in the use of praziquantel for treatment of human trematode and cestode infections are briefly reviewed. Since praziquantel was first introduced as a broadspectrum anthelmintic in 1975, innumerable articles describ- ing its successful use in the treatment of the majority of human-infecting trematodes and cestodes have been published. The target trematode and cestode diseases include schistosomiasis, clonorchiasis and opisthorchiasis, paragonimiasis, het- erophyidiasis, echinostomiasis, fasciolopsiasis, neodiplostomiasis, gymnophalloidiasis, taeniases, diphyllobothriasis, hyme- nolepiasis, and cysticercosis. However, Fasciola hepatica and Fasciola gigantica infections are refractory to praziquantel, for which triclabendazole, an alternative drug, is necessary. In addition, larval cestode infections, particularly hydatid disease and sparganosis, are not successfully treated by praziquantel. The precise mechanism of action of praziquantel is still poorly understood. There are also emerging problems with praziquantel treatment, which include the appearance of drug resis- tance in the treatment of Schistosoma mansoni and possibly Schistosoma japonicum, along with allergic or hypersensitivity
    [Show full text]