James Gaensbauer, MD MScPH October 18, 2016

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1 James Gaensbauer, MD MScPH October 18, 2016 Pediatric Infectious Diseases, University of Colorado School of Medicine Center for Global Health, Colorado School of Public Health Denver Health Hospital Authority Denver Metro Tuberculosis Clinic

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3 Protozoa first animals Platyhelminths flat worms Nematodes thread (roundworms) Acanthocephala thorny headed Arthropods jointed feet

4 Protozoa Platyhelminths Cestodes Nematodes Trematodes (flukes) Intestinal Entamoeba Giardia Cryptosporidium Taenia (ingested larvae) Diphyllobothrium Ascaris Hookworms Strongyloides Trichuris Tissue/Blood Malaria Leishmania Naeglaria Toxoplasma Taenia/cysticercosis (ingested eggs) Echinococcus Schistosoma Fasciola Clonorchis Trichonella Druncunculus Angiostrongylus Filaria

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6 Ascaris Hookworm Acute Effects Pulmonary Hypersensitivity Bile duct obstruction Liver abscess Intestinal obstruction Ground Itch Abdominal Pain Chronic Effects Malabsorption Nutritional deficency Growth Retardation Congnitive delay Anemia Cognitive Delay Trichuris Trichuris Dysentery Nutritional deficiency Growth retardation Cognitive Delay

7 Schistosomiasis Acute Effects Febrile illness Bloody stools Hematuria Enlarged liver and spleen Chronic Effects Anemia Impaired growth Liver failure Kidney failure

8 Burden of Intestinal Parasitic Infection Soil Transmitted Helminths Ascaris 1 billion Hookworms 740 million Trichuris Soil Transmitted Helminths 795 million Strongyloides billion million Cestodes 740 million Taeniasis million Cysticercosis million million (50,000 deaths/year) Cestodes Protozoa Giardia 2% adult/8% 2.5 million children Entamoeba million Cryptococcus (50,000 >1 deaths/year) billion Ascaris Hookworms Trichuris Strongyloides Taeniasis Cysticercosis Giardia Entamoeba Cryptococcus Protozoa 2% adult/8% children 50 million >1 billion WHO 2012; Hotez 2008, CDC 2012

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11 Immune Responses to Helminth Infection Pathogen Killing Tissue Damage Parasite IFN- IL-17 IL-4 Th2 Th1 x IL-10 Immune Modulation Protective Immunity Tissue Healing

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13 Yazdanbakhsh, 2002

14 Viral HIV Bacterial Cholera Tuberculosis Parasitic Malaria Vaccine Immunity? Cholera vaccine BCG Tetanus Numerous Animal models

15 A 4 year old girl with hx of asthma presents to your local rural hospital in Paraguay with abdominal pain and distension. She has vomited everything she has eaten and has not passed stool in 4 days. Today her belly feels firm, and she is acting ill.

16 You get an X ray and note dilated loops of intestine with air fluid levels. Ultrasound notes a mass in her ileum. Surgery removes complete obstruction by a bolus of ascaris worms. You tx with albendazole and she shows full recovery.

17 Ingest eggs Larvae invade intestines Lung GI tract Excrete eggs

18 Clinical Manifestions Lung: Loeffler s syndrome mimics asthma GI tract: Malabsorption/malnutrition: Vitamin A, Fe Obstruction Children ileal, appendiceal mimics obstruction, intussusception, volvulus, appendicitis Adults: hepatobiliary, pancreatic obstruction mimics cholecysitis, pancreatitis Worms migrate with high fever or anesthesia Screen before elective surgery in endemic area

19 Diagnosis: Stool O+P Imaging: Ultrasound, Endoscopy Treatment: Medical: Albendazole X 1 Mebendazole X 1 (only for Ascaris) If obstruction: piperzine citrate relaxes worms Surgery/ERCP: removal of obstruction

20 You conduct a school visit at an elementary school on an island in Lake Victoria, Kenya. You note that the children are barefoot and play in the shallow water on the sandy coastline. There are no public latrines and the children run to the lake to defecate. The children in the school appear pale, malnourished, some are chewing on rocks, soil.

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22 Penetrate skin Lungs GI tract Attach Excrete Eggs

23 Skin penetration: Ground itch Lung: eosinophilic pneumonitis GI tract: Intestinal attachment blood loss Fe deficiency anemia, Pica Hypoproteinemia and anasarca

24 Necator americanus Adult worms use cutting apparatus to attach to intestinal mucosa Contract muscular esophagi to create negative pressure and suck tissue plug Hydrolytic enzymes, mechanical disruption of blood vessels causes bleeding

25 Diagnosis: Stool O+P Treatment: Albendazole X 1 Mebendazole X 3 days Consider Fe/Micronutrient supplementation

26 A 10 year old female presents for checkup and vaccinations in your mobile clinic on the islands of Lake Victoria. She has recently noted blood in her urine, which she had attributed to starting her menses. She does not attend school because she helps her mother fishmongering on the beach.

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28 Host: freshwater snails Penetrates skin Blood dwelling fluke Matures in portal vein Migrates to preferred body part (based on species) and releases eggs Bladder/ GU tract GI tract Eggs excreted in urine or stool

29 Skin: swimmer s itch Acute: Katayama Fever (systemic) hypersensitivity rxn against production of eggs 4 8 weeks after exposure Fever, headache, myalgias, bloody diarrhea, tender hepatomegaly Chronic: eggs trapped in tissues secrete enzymes causing eosinophilic inflammation, granulomas

30 Bladder/GU tract: S. haematobium Hematuria of terminal urine, dysuria, proteinuria Fibrosis, calcification > hydronephrosis, RF Squamous bladder cancer GI tract: S. mansoni, S. japonicum Chronic colicky abdominal pain, diarrhea, bloody stools Liver: S. mansoni, S. japonicum Pipestem fibrosis, cirrhosis, liver failure

31 Diagnosis Stool O+P Filtered urine microscopy Urine strips for hematuria in highly endemic area Treatment Praziquantel Add steroids in Katayama fever, and repeat dose of praziquantel 4 6 weeks afterwards

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33 Deworming programs Development based approaches Education/Awareness Vaccine

34 Local epidemiology: Spectrum of parasitic etiologies Local parasite burden: Kato Katz method of quantification Number of infected individuals Number of highly infected individuals Resources Existing Programs

35 Periodic Therapy Universal Targeted Selective Frequency Target Age Medication Benzimidazoles +/ Praziquantil Vitamin A supplementation Monitoring

36 Universal impact varies Greatest improvements occur when: Hookworm is a predominant parasite and anemia is the primary outcome Iron and Vitamin A supplementation complement deworming Treatment begins at early age Doses are given 3 times/year vs. 2 in high prevalence areas

37 Improved sanitation Prevention of fecal contamination of food and water supply Hygiene Education Economic development

38 Molecular diagnosis Vaccination New anti helminth medications Outside the box strategies (eg. Wolbachia)

39 22 year old male Previously well Suffered a focal seizure with secondary generalization No prior history of seizures, no family history of epilepsy Emigrated from Honduras at age 19 Normal physical and neurologic exam

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41 Neurocysticercosis Tumor Brain Abscess

42 Taeniasis: asymptomatic pork tapeworm carriers Ingest undercooked infected pork with cysticerci Adult tapeworms reside in small intestine Excrete eggs in stool proglottids

43 Cysticercosis: Ingestion of humanexcreted eggs (not pork) Eggs hatch, oncospheres invade intestine, travel thru bloodstream lodge in tissues: subcutaneous, muscles, eye, brain

44 Caused by cystic larvae of pork tapeworm: Taenia Solium ~50 million infected worldwide, more than 400,000 with neurologic symptoms in Latin America alone Most common cause of acquired epilepsy in the developing world Endemic to areas of Central and South America, Africa, India, Asia Increasingly recognized in US in immigrant population 10% of adult pts with seizures presenting to an ED in LA

45 Tissue cysticerci develop 3 8 weeks after ingestion of eggs, initially elicit few inflammatory changes Lay dormant for years, peak sx onset 3 5 yrs Cysts degenerate immune mediated Inflammation Intraparenchymal: Seizures, headaches Extraparenchymal: Hydrocephalus, increased ICP Eventually either resolve or form calcified granulomas

46 Stages of Neurocysticercosis Lesions A. Viable cyst B. Viable cyst with initial signs of inflammation scolex C. Degenerating cyst D. Calcified granulomas Garcia et al. 2004

47 Decision to treat must be considered carefully Rule out eye involvement with ophtho exam If encephalophathic or diffuse edema, steroids alone Treatment regimen consists of: Antiepileptics X 6 12 months, trial off Antiparasitic: Albendazole 15mg/kg/day div bid X 7 14 days (max 800mg/day) Corticosteroids: 1mg/kg prednisone or 0.1mg/kg decadron daily X 5 10 days If hydrocephalus, increased ICP consider surgery

48 29 y.o. pediatric resident Diarrhea 1 week after returning from rural Guatemala, has persisted for 10 days 3 5 watery stools/day No pus or blood No fever, chills Exam notable for bloating, mild tenderness, not dehydrated

49 Giardia Differential?

50 Cryptosporidium common, cattle water human. Worse with immune compromise Entamoeba: Diarrhea, dysentery, can have extra intestinal manifestations (e.g. abscess) Isospora, Microspora, Cyclospora (AIDS)

51 Travel to countries where giardiasis is common Child care settings Close contact with infected individual Swallowing contaminated drinking water Contact with infected animals Men who have sex with men

52 Giardia Life Cycle Source: CDC 2014

53 Diarrhea Gas Greasy stools that tend to float Stomach or abdominal cramps Upset stomach or nausea/vomiting Dehydration (loss of fluids Fever and systemic manifestations rare

54 O + P?

55 Wet Mount Fixed Concentrated/Stained Stool Antigen Test Duodenal String Test PCR

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57 Metronidazole (Flagyl) most common/ first line Nitazoxanide (Alinia) Tinidazole Albendazole

58 Balantium coli Blastocystis hominis Entamoeba coli (and others) Endolimax nana Helminths: rare if ever causes of diarrhea (perhaps Strongyloides)

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