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Soil-Transmitted Helminths Elaine C. Jong MD Clinical Professor of Medicine University of Washington Infectious Diseases Travel & Tropical Medicine [email protected] April, 2013 Helminth Infections: Magnitude Of The Problem Ascaris, Enterobius Trichuris, hookworm Schistosomiasis Filariasis (W. bancrofti) Strongyloides Paragonimus Onchocerciasis Loa loa Opisthorchis Clonorchis Fasciola hepatica 1 billion infections each 500-900 million each 200 million 115 million 50-100 million 21 million 17.8 million 3-13 million 10 million 7 million 2 million Worm Kingdom • Nematodes= Roundworms • Ascaris lumbricoides (common roundworm) • Ancylostoma duodenale and Necator americanus (hookworm) • Trichuris trichiura (whipworm) • Strongyloides stercoralis • Enterobius enterobium (pin worm) • Cestodes= Tapeworms • Trematodes= Flukes Questions • What are the main risk factors for soiltransmitted helminths (STH)? • What are some of the impacts of STH on human health? • What are effective interventions to interrupt the transmission of disease? • What is the accepted approach to diagnosis and treatment of STH in less-developed areas where such infections are highly endemic? • How does this differ from the usual standard of care in the United States? Overview: Helminth Infections • May be asymptomatic • May be an incidental finding in lab exam of clinical specimens • Symptoms and disease usually associated with heavy worm burdens • With a few exceptions, most worms are unable to multiply in their host • Heavy worm burdens therefore tend to be the result of repeated infections over time • Worms can live for years in a human host— >20 years in the case of certain flukes Overview: Helminth Infections-2 • May be associated with gastrointestinal symptoms: • diarrhea, abdominal discomfort, abnormal stools, rectal irritation/ itching • May cause malnutrition and pediatric growth retardation in endemic areas • May affect productivity in adulthood • May be associated with striking peripheral blood eosinophilia • during larval migratory stages, or • location of either adult worms or eggs in tissues outside the intestinal lumen STH Transmission Helminth infections, growth, and anemia Transmission of helminth infection Accumulation of worm burden • Malabsorption • Gastrointestinal blood loss • Chemical messages to host Irondeficiency anemia Poor growth Poor cognitive development Adapted from Chwaya HM, Stoltzfus RJ. In: Drompton DWT et al (eds), Controlling disease due to helminth infections. Geneva, WHO, 2003. p.34 1.3 billion Ascaris infections worldwide Source: de Silva NR et al., 2003. TRENDS in Parasitology.19:547-551 Ascaris Infections Ascaris lumbricoides—common helminth infection with ~1.3 billion persons infected • 71% in Asia: China, India, SE Asia • 13% in Latin America & Caribbean • 8% sub-Saharan Africa • Eggs relatively resistant to drying or extremes of temperature • Larvae migrating through the lungs cause eosinophilic inflammation • Heavy worm burdens in children may cause intestinal obstruction • Migrating and ectopic worms: intestinal perforation, bile duct obstruction, peritonitis, appendicitis, etc. Source: Jong EC, Stevens, DA. (eds) Netter’s Infectious Diseases 1e, Elsevier, 2012. From: Teaching Slide Collection, Medical Parasitology, Markell & Voege Ascaris adults DPDx-CDC: www.dpd.cdc.gov./dpdx Courtesy of Prof. E.C.Jong DPDx-CDC: www.dpd.cdc.gov./dpdx 500-900 million hookworm infections worldwide Source: de Silva NR et al., 2003. TRENDS in Parasitology.19:547-551 HOOKWORM INFECTIONS • Iron-deficiency anemia is the hallmark of chronic hookworm disease • Adult hookworms inhabit the upper half of the small intestine • Attach and suck blood with the aid of an organic anticoagulant • Ancylostoma duodenale = 0.15- 0.26 mL/ day/ worm • Necator americanus = 0.03 mL/ day/ worm • Additional blood loss from bleeding at sites of attachment • Blood loss and compensatory volume expansion • Microcytic hypochromic anemia • Hypoalbuminemia • Cardiovascular changes in severe cases Source: Jong EC, Stevens, DA. (eds) Netter’s Infectious Diseases 1e, Elsevier, 2012. Hookworm Symptoms • Pruritic erythema (“Ground Itch”) • Pulmonary symptoms during larval migration to the gut • Transient gastroenteritis-like syndrome as adult hookworms attach to the intestinal mucosa • Eosinophila noted in 30-60% of infected patients Who’s who? 500-900 million whipworm infections worldwide Source: de Silva NR et al., 2003. TRENDS in Parasitology.19:547-551 Whipworm Infections • 500-900 million Trichuris trichiura infections worldwide • Approximately same distribution as Ascaris • Ingestion of eggs in contaminated vegetables or soil • Inhabit the caecum & colon causing inflammation, hemorrhagic patches • Each female worm produces ~10,000 eggs per day passed in the feces • Heavy infection can cause growth retardation, malnutrition, rectal prolapse Source: Jong EC, Stevens, DA. (eds) Netter’s Infectious Diseases 1e, Elsevier, 2012. Trichuris trichiura adult female Source: CDC Parasitology Diagnositic Web Site http://www.dpd.dcd.gov/dpdx Strongyloides infections • Strongyloides stercoralis causes chronic infections that are often silent • Elevation of peripheral blood eosinophils • Soil transmitted life cycle • Autoinfection life cycle • Can complete life cycle without leaving the human host • Filariform larvae in fecal stream may penetrate perirectal skin causing rash “cutaneous larva currens” • Infection may be self-perpetuating for decades after leaving endemic area • Hyperinfection occurs in immune-compromised hosts • Dissemination with local inflammation, enteritis, pneumonitis, microabscesses Source: Jong EC, Stevens, DA. (eds) Netter’s Infectious Diseases 1e, Elsevier, 2012. Patient with cutaneous larva currens rash Courtesy of Prof. E.C.Jong From: Teaching Slide Collection, Medical Parasitology, Markell & Voege Strongyloides stercoralis filariform larva Source: CDC Parasitology Diagnositic Web Site http://www.dpd.dcd.gov/dpdx Enterobius vermicularis • Ubiquitous infection of children (estimated 1.3 billion infections worldwide) • Adults live in the caecum, gravid females migrate to the rectal area at night • Common cause of perianal itching • Appendicitis • Peritonitis • Vulvovaginitis • Eggs mature after 4-6 hours outside intestine and become infective • Fecal-oral spread on fingers and fingernails Source: Jong EC, Stevens, DA. (eds) Netter’s Infectious Diseases 1e, Elsevier, 2012. Clinical Summary: Soil-Transmitted Helminths • Light infections may be asymptomatic • Heavy worm burdens may be associated with • Gastrointestinal symptoms: diarrhea, abdominal discomfort, abnormal stools, rectal irritation/ itching • Malnutrition, pediatric growth retardation, and anemia: resulting from malabsorption and gastrointestinal blood loss • Cognitive impairment Clinical Summary: STH, p.2 • Infections may be associated with striking peripheral blood eosinophilia • Larval migratory stages • Location of either adult worms or eggs in tissues outside the intestinal lumen • Infections do not lead to protective immunity • Heavy worm burdens usually acquired from repeated exposure in contaminated environments • Children acquire heavy worm burdens from contact with the ground and poor hygiene • Strongyloidiasis is unique—once infected, worm burdens may persist/ increase through autoinfection cycle Parasite Diagnosis • Identification of gross specimens • Stool for ova & parasite microscopic exam • Wet mount • Trichrome stain • Serology tests • Not for routine STH diagnosis • May be useful for extraintestinal helminthic infections • Strongyloidiasis (Strongyloides stercoralis) • Trichinosis (Trichinella spiralis) • Toxocara canis/ catis Drugs for STH Treatment DRUG Ascaris Pyrantel pamoate (Antiminth)¹ √ Mebendazole (Vermox)² √ √ √ Thiabendazole (Mintezol)³ (√) √ √ √ Albendazole (Albenza)ª √ √ √ √ Ivermectin (Stromectol)§ Trichuris Hookworm Strongyloides √ √ (intestinal stages only) ¹Paralysis of worm nervous system; ²Inhibition of microtubules, glucose depletion; ³Inhibition of helminth-specific fumarate reductase; ªInhibition of cytoplasmic microtubules; § bind glutamate-gated chloride ion channels increasing membrane permeability to chloride ions resulting in paralysis WHO (1997) MODEL LIST OF ESSENTIAL DRUGS FOUR ANTIPARASITIC DRUGS LISTED: • Albendazole • Levamisole • Mebendazole • Pyrantel pamoate www.who.int Individual Diagnosis & Treatment • Stool ova and parasite exam (O&P) • Treat with drug of choice • Best drug available • FDA-approved, off label use • Investigational new drug protocol/ orphan drug • Repeat O&P for test of cure or fecal egg count reduction (FECR) 4 or more weeks after therapy WHO community treatment (May 2001, resolution 54.19) • “Deworming campaigns” involve presumptive treatment of high-risk groups • Routine screening of stool specimens is labor-intensive and not practical in many settings • Use of WHO drugs at de-worming doses associated with negligible and self-limiting side effects • Target high risk groups (school-age children & women of child-bearing age) (selective treatment) • Treat all persons (mass treatment) with “preventive chemotherapy” in particular regions • Survey for severe adverse reactions related to the widespread distribution of antihelminthic drugs Summary of STH Prevention • Hand washing • Wearing shoes • Behavior/ education • Personal hygiene • Geophagia • Latrines • Individual treatment • Targeted mass treatment Articles • Andrade C, Alava T, De Palacio IA, et al. Prevalence and intensity of soil-transmitted helminthiasis in the city of Portoviejo (Ecuador). Mem Inst Oswaldo Cruz, 96:1075-9, 2001. • Glickman LT, Camara AO, Glickman NW, et al. Nematode intestinal parasites of children in rural Guinea, Africa: prevalence and relationship to geophagia. Int J Epidemiol, 28:169-74, 1999. • Guyatt HL, Brooker S, Kihamia CM, et al. Evaluation of efficacy of school-based anthelmintic treatments against anaemia in children in the United Republic of Tanzania. Bull World Health Organ, 79:695-703. Epub 2001 Oct 24. • Kawai K, Saathoff E, Antelman G, et al. Geophagy (Soil-eating) in relation to anemia and helminth infection among HIV-infected pregnant women in Tanzania. • Kirwan P, Asaolu SO, Molloy SF, et al. Patterns of soil-transmitted helminth infection and impact of four-monthly albendazole treatments in preschool children from semi-urban communities in Nigeria: a double-blind placebo-controlled randomised trial. BMC Infect Dis. 2009;9:20. • Ndyomugyenyi R, Kabatereine N, Olsen A, et al. Efficacy of ivermectin and albendazole alone and in combination for treatment of soil-transmitted helminths in pregnancy and adverse events: a randomized open label controlled intervention trial in Masinid district, western Uganda. Am J Trop Med Hyg. 2008; 79:856-63. • Steinman P, Utzinger J, Du Z-W, et al. Efficacy of single-dose and triple-dose albendazole and mebendazole against soil-transmitted helminths and taenia spp.: a randomized controlled trial. PLoS ONE. 2011; 6(9): e25003. doi:10.1371/jounal.pone.0025003. • Vercruysse J, Behnke JM, Albonico M, et al. Assessment of the antihelminthic efficacy of albedazole in school children in seven countries where soil-transmitted helminths are endemic. PLoS Negl Trop Dis. 2011; 5(3): e949. doi: 10.1371/journal.pntd.0000948. • Watson JL, Herrin BR, John-Stewart G. Deworming helminth coinfected individuals for delaying HIV disease progression. Cochrane Database Syst Rev. 2009; (3):CD006419. • Ziegelbauer K, Speich B, Mäusezahl, et al. Effect of sanitation on soil-transmitted helminth infection: systematic review and metaanalysis. PLoS Med. 2012; 9(1):e1001162. doi:10.1371/journal.pmed.1001162.