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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 Onchocerca volvulus Loa loa Lung flukes Trichinella spiralis Schistosoma > 150 million Paragonimus westermani Angiostrongylus cantonensis Anisakis simplex Intestinal flukes Toxocara canis/cati Gnathostoma spinigerum Fasciolopsis buski (Dirofilaria repens) Metagonimus yokagawai (Baylisascaris procyonis) http://ghdx.healthdata.org/gbd-data-tool ID Board Prevalance Question #1 Low 28 yo F presents with recurrent crampy abdominal pain for several months. She recently returned to the U.S. after living in Tanzania for two years. Parasitology typically about 5% of board exam Colonoscopy reveals small white papules. Biopsy of a papule reveals an egg with surrounding granulomatous inflammation. Most likely diagnosis? In addition to all helminths, includes: A. Entamoeba histolytica B. Strongyloides stercoralis • Protozoa C. Wuchereria bancrofti • Ectoparasites D. Schistosoma mansoni • Principles of Travel Medicine E. Paragonimus westermani Major Helminth Pathogens Trematodes (flukes) TREMATODES CESTODES NEMATODES Blood flukes Intestinal tapeworms Intestinal • flat, fleshy, leaf-shaped worms Schistosoma mansoni Taenia solium Ascaris lumbricoides Taenia saginata Ancylostoma duodenale Schistosoma japonicum Necator americanus Schistosoma haematobium Diphyllobothrium latum Trichuris trichiura (Hymenolepis nana) Strongyloides stercoralis • usually have two muscular suckers Paragonimus (CDC DpDx) Liver flukes Enterobius vermicularis Fasciola hepatica Larval cysts Taenia solium Tissue Invasive Clonorchis sinensis Echinococcus granulosus Wuchereria bancrofti • usually hermaphroditic (except Schistosomes) Brugia malayi Opisthorchis viverrini Echinococcus multilocularis Onchocerca volvulus Loa loa Lung flukes Trichinella spiralis • require intermediate hosts (usually snails or clams) Paragonimus westermani Angiostrongylus cantonensis Anisakis simplex Intestinal flukes Toxocara canis/cati (Gnathostoma spinigerum) Fasciolopsis buski (Dirofilaria repens) • praziquantel treats all (except Fasciola hepatica) Metagonimus yokagawai (Baylisascaris procyonis) ©2021 Infectious Disease Board Review, LLC 62 –Worms and More Worms Speaker: Edward Mitre, MD Schistosomiasis life cycle Acute Schistosomiasis (Cercarial dermatitis or Swimmer’s Itch) Urticarial plaques and pruritic papules upon reexposure to cercariae penetrating skin in a sensitized individual. Can occur in response to human or avian schistosomes. Acute Schistosomiasis: Katayama Fever Schistosomiasis • Occurs in previously unexposed hosts. Chronic disease granulomatous colitis (S. mansoni) • Occurs at onset of egg-laying (3-8weeks) portal hypertension (S. mansoni) • Symptoms: fever, myalgias, abdominal pain, headache, granulomatous cystitis (S. haematobium) diarrhea, urticaria bladder fibrosis and cancer (S. haematobium) obstructive uropathy (S. haematobium) • Eosinophilia, AST, alkaline phosphatase CNS disease (eggs to brain/spinal cord, esp S. japonicum) • No reliable way to confirm the diagnosis acutely as serology and stool O/P frequently negative. Schistosomiasis Schistosome eggs Chronic genital disease S. mansoni increasingly recognized (lateral spine) primarily due to S. haematobium sand grains sandy yellow patches men - epididymitis - prostatitis CDC DPDx image library women (see vaginal and cervical lesions) - pelvic pain - dysmenorrhea S. haematobium - dyspareunia abnormal vessels rubbery papules - post-coital bleeding (terminal spine) - endometritis/salpingitis WHO Female Genital Schistosomiasis Pocket Atlas CDC DPDx image library ©2021 Infectious Disease Board Review, LLC 62 –Worms and More Worms Speaker: Edward Mitre, MD When to consider Schistosomiasis Major Helminth Pathogens TREMATODES CESTODES NEMATODES Blood flukes Intestinal tapeworms Intestinal • Fresh water exposure in an endemic region. Schistosoma mansoni Taenia solium Ascaris lumbricoides Taenia saginata Ancylostoma duodenale Schistosoma japonicum Necator americanus Schistosoma haematobium Diphyllobothrium latum Trichuris trichiura • Clinical syndrome compatible with acute schistosomiasis (Hymenolepis nana) Strongyloides stercoralis Liver flukes Enterobius vermicularis (F, abd pain, myalgias, eosinophilia) Fasciola hepatica Larval cysts Taenia solium Tissue Invasive Clonorchis sinensis Echinococcus granulosus Wuchereria bancrofti Brugia malayi Opisthorchis viverrini Echinococcus multilocularis Onchocerca volvulus • Clinical syndrome compatible with chronic Loa loa Lung flukes Trichinella spiralis schistosomiasis (abdominal/pelvic pain, blood in stool, Paragonimus westermani Angiostrongylus cantonensis loose stools, evidence of portal HTN, hematuria, Anisakis simplex Intestinal flukes Toxocara canis/cati eosinophilia) Gnathostoma spinigerum Fasciolopsis buski (Dirofilaria repens) Metagonimus yokagawai (Baylisascaris procyonis) Fasciola hepatica (a liver fluke) Clonorchis sinensis Opisthorchis viverrini acquired by eating encysted larvae on aquatic vegetation (e.g. water chestnuts) “Chinese Liver Fluke” “Southeast Asian Liver Fluke” • eggssnailsfreshwater fish fluke migration through the liver: RUQ pain and hepatitis • Acquisition by ingestion of undercooked fish • similar lifecycle • Flukes develop in duodenum then migrate to • also acquired by eating fish arrive at biliary ducts in liver and mature over 3-4 months liver bile ducts • Can live for 50 years, making 2000 eggs/day can induce biliary obstruction Both can cause Dx: eggs in stool exam (low sensitivity), serology biliary obstruction cholelithiasis Rx: triclabendazole (FDA approved in 2019!) (***note: the only trematode that don’t respond well to praziquantel) cholangiocarcinoma Paragonimus westermani “lung fluke” Intestinal Flukes eggssnailsfreshwater crabs and crayfish Fasciolopsis buski Ingestion of undercooked seafood (“Giant Intestinal Fluke” 2cm w x 8 cm) Adults migrate to LUNGS, frequent EOSINOPHILIA CDC • acquisition: eating encysted larval stage on aquatic vegetation Symptoms: • symptoms: usually asymptomatic • fever, cough, diarrhea during acute migration • can cause diarrhea, fever, abdominal pains, ulceration, and hemorrhage • later, may have chest pain as worms migrate through lungs • can develop chronic pulmonary symptoms Dx: eggs in stool Dx: Sputum and/or stool exam for eggs. Metagonimus yokagawi NOTE: Cases of Paragonimus kellicotti acquired in U.S. by ingestion of raw (2.5mm x 0.75mm) crayfish in rivers in Missouri • acquisition: eating larvae in undercooked fish CID 2009 Sep 15;49(6):e55-61. Clin Microbiol Rev 2013 Jul;26(3):493-504 • symptoms: diarrhea and abdominal pain ©2021 Infectious Disease Board Review, LLC 62 –Worms and More Worms Speaker: Edward Mitre, MD Question #2 Major Helminth Pathogens TREMATODES CESTODES NEMATODES A 25 yo F reports passing thin, white, flat tissue fragments in her stool several Blood flukes Intestinal tapeworms Intestinal times over the past few weeks. She is healthy and has been in Madagascar Schistosoma mansoni Taenia solium Ascaris lumbricoides Ancylostoma duodenale for 3 years as a Peace Corps volunteer. The microbiology lab confirms the Schistosoma japonicum Taenia saginata tissue fragments are parts of a helminth. Necator americanus Schistosoma haematobium Diphyllobothrium latum Trichuris trichiura (Hymenolepis nana) Strongyloides stercoralis A long-term complication that can occur as a result of infection with certain Liver flukes Enterobius vermicularis Fasciola hepatica Larval cysts species of this type of helminth is: Taenia solium Tissue Invasive Clonorchis sinensis Echinococcus granulosus Wuchereria bancrofti Brugia malayi Opisthorchis viverrini Echinococcus multilocularis A. HTLV-1 infection Onchocerca volvulus Loa loa Lung flukes B. bladder cancer Trichinella spiralis Paragonimus westermani Angiostrongylus cantonensis C. appendicitis Anisakis simplex Intestinal flukes Toxocara canis/cati D. liver abscess Gnathostoma spinigerum Fasciolopsis buski (Dirofilaria repens) E. seizures Metagonimus yokagawai (Baylisascaris procyonis) INTESTINAL TAPEWORMS
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  • Against Laboratory Models of Human Intestinal Nematode Infections

    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.