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LUMC Course Parasitology ESCMID Online Lecture Library © by Author Giardia lamblia and Dientamoeba fragilis clinical aspects, diagnostics and epidemiology © Theoby Mankauthor ESCMID Online Lecture Library LUMC course parasitology Dientamoeba © by author ESCMID Online Lecture Library LUMC course parasitology Giardia lamblia the parasite that keeps surprising © by author ESCMID Online Lecture Library LUMC course parasitology Giardia lamblia • 1681: Giardia was first observed by Anthony van Leeuwenhoek, the pioneering microscopist from Delft, The Netherlands, in his watery stools • Late 70s: Giardia was recognized as a human pathogen, based on symptoms such as malabsorption and the pathology observed in the upper part of the small intestine in patients from whom the organism was isolated (Koulda and Nohynova 1978) • 1981: The World Health© Organization by author added Giardia to its list of parasitic pathogens • ESCMID2006: Giardia was Online added to the LectureWHO “Neglected Library Disease Initiative” (Savioli et al, 2006) LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology Prevalence • Cosmopolitan • Depending on the population – Higher in case of suboptimal sanitation – Quality of drinking water – Developing countries© by author ESCMID– Day care centers Online Lecture Library – Personal hygiene LUMC course parasitology The Netherlands total population 16 million © by author ESCMID Online Lecture Library LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology water in The Netherlands © by author ESCMID Online Lecture Library LUMC course parasitology Prevalence NL • Depending on the population – Asymptomatic carriership 2-3% • N=360.000 – Duration of complaints© by author • acute GI in general practice ± 5% • persistent diarrhea in GP ≥ 1week ± 14% ESCMID Online Lecture Library – HospitalizedLUMC < General course Practice parasitology Age-distribution (N=892 patients; numbers represent percentages) 30 25 Cryptosporidium spp 20 D. fragilis G. lamblia 15 C. jejuni Salmonella spp 10 © by author 5 ESCMID Online Lecture Libraryp<0.01 0 p<0.01 1-4LUMC 5-14 course 15-24 25-45 parasitology 45-65 Seasonal distribution (N=892 patients; numbers represent percentages) 18 p<0.01 16 14 Cryptosporidium spp 12 D. fragilis 10 G. lamblia 8 © by author C. jejuni 6 Salmonella spp 4 ESCMID2 Online Lecture Library 0 WinterLUMC Spring courseSummer parasitology Autumn The “natural course“ of Giardia What happens after ingestion of the cysts? © by author ESCMID Online Lecture Library LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology © by author ESCMID Online Lecture Library LUMC course parasitology Clinical presentation spectrum disease • Asymptomatic / beneficial • Mild; intermittent, not comfortable • Acute diarrhoea © by author • Chronic; persistent diarrhea, brush border abnormalities, malabsorption (children: failure to ESCMIDthrive / impaired Online cognitive Lecture development) Library LUMC course parasitology “some people benefit from their carrier state” • Observation: asymptomatic carriers in day care centers in Israel tended to have fewer symptoms related to GI- and respiratory tracts as compared to Giardia free children (Ish-Horowicz et al Asymptomatic giardiasis in children. the Journal of Infectious Diseases 1987;156:974-84) • Observation: asymptomatic giardiasis in rural Tanzanian children “protects” against diarrhea (J Veenemans, T Mank, M Ottenhof etal© Protection by against author diarrhea associated with Giardia intestinalis is lost with multi-nutrient supplementation: a study in Tanzanian Children. Plos Neglected Tropical Diseases, Research Article published 7 juni 2011 10.1371/journal.pntd 00158 ESCMID Online Lecture Library LUMC course parasitology Study Population and Design Study period: February 2008 - March 2009 Location: Kwedizinga ward, Tanzania (malaria endemic) Study population: children aged 6-60 months They randomly received daily oral supplement: - Zinc - Multinutrients with zinc - Multinutrients without zinc Zinc - Placebo Multinutrients Parents or caretakers were asked to bring their Multinutrients children immediately to the research dispensatory with zinc Placebo when they observed fever, diarrhoea or any other signs of illness. © by author Blood sample collection: at the start and at the end of the intervention, and at the time of fibrile attack. Stool sample collection: ESCMID at the start and at a median Online of 251 days of intervention.Lecture Library Intervention Groups LUMC course parasitology Invited for screening N=1265 No show N=236 Screened N=1029 Excluded (n=417) - Parents refused consent: 21 - Height-for-age >-1.5 SD: 359 - Medical reasons: 13 - Date of birth unclear: 8 Eligible - Unlikely to comply with intervention: 18 N=612 Multi-nutrients Multi-nutrients Zinc Placebo without zinc with zinc N=153 N=153 N=155 N=151 © by author Lost to follow- Lost to follow- Lost to follow- up: 3 Lost to follow- up: 5 up: 3 Refused: 1 up: 4 Refused: 1 Died: 2 ESCMID Online Lecture Died:Library 1 Completed Completed Completed Completed N=147 (96%) LUMCN=150 course(97%) parasitologyN=146 (97%) N=149 (97%) Complied: Complied: Complied: Complied: N=145 (95%) N=148 (95%) N=146 (97%) N=148 (97%) © by author ESCMID Online Lecture Library LUMC course parasitology Giardia infection at baseline protects against subsequent diarrhoea… 1.00 P <0.001 0.75 © by author Infected ESCMID OnlineNon-infected Lecture Library 0.50 LUMC course parasitology 0 100 200 300 400 Time to first reported episode of diarrhoea …but not when receiving multinutrients 1.00 Infected Non-infected 0.75 © by author Analysis restricted to children who ESCMID Onlinereceived Lecture multinutrients Library (with or without zinc) 0.50 LUMC course parasitology 0 100 200 300 400 Time to first reported episode of diarrhoea Association between Giardia infection at baseline and subsequent diarrhoea… 1.00 Placebo or zinc; Giardia + Multinutrients 0.75 ; Giardia + Multinutrients; © by author Giardia – Placebo or zinc; Giardia – ESCMID Online Lecture Library 0.50 LUMC course parasitology 0 100 200 300 400 Clinical presentation spectrum disease • Asymptomatic / beneficial • Mild; intermittent, not comfortable • Acute diarrhea (travellers) © by author • Chronic; persistent diarrhea, brush border abnormalities, malabsorption (children: failure to ESCMIDthrive / impaired Online cognitive Lecture development) Library LUMC course parasitology Compaints in symptomatic giardiasis • diarrhoea (persistent or intermittent) • frothy, greasy, smelly, sticky stools / floats on water • bloating • flatulence • abdominal pain • upper intestinal cramps • nausea © by author • vomiting ESCMID• anorexia Online Lecture Library • weight loss or reduced weight gain • feverishLUMC course parasitology Clinical presentation spectrum disease • Extra intestinal manifestations include: – Arthritis – Aphtous ulcerations – Biliary tract ©disease by author – Urticaria – Sensitisation towards food allergens ESCMID– Ocular Onlinedisorders (uveitis, Lecture retinal Libraryarteritis) – MicronutrientLUMC course deficiencies parasitology (Fe, Zn, Vit A, Vit B12) © by author ESCMID Online Lecture Library LUMC course parasitology “risk factors” chronic giardiasis • Host related factors • Immune status • Hypogammaglobulinemia (IgA def) • Age • Nutritional status © by author • Parasite related ESCMID• Number Online of cysts ingested Lecture Library • Genotype LUMC course parasitology Species and genotypes of Giardia spp © by author ESCMID Online Lecture Library LUMC course parasitology Molecular characterization of Giardia Targets (PCR-RFLP / sequencing / MLST) – 18s rDNA – GdH (glutamate dehydrogenase) – ß-giardine – tpi (triose phosphate isomerase) – Elongationfactor©-1α by author – GLORF-C4 (G lamblia open reading frame C4) ESCMID Online Lecture Library LUMC course parasitology Relationship of Giardia based on GDH locus © by author ESCMID Online Lecture Library LUMC course parasitology Ey et al, 1997 human Giardiasis • G duodenalis assemblage A & B only • Several studies on genotype in relation to clinical presentation have been performed • Controversial conclusions • differences in© study by design author • in- and exclusion criteria • other diarrheal agents tested for (eg bacterial / viral) ESCMID• multiplex Online PCR format /Lecture Luminex technology Library LUMC course parasitology Therapy First line: 5-nitro-imidazole derivates metronidazol / Flagyl® adults: 500 mg tid x 7-10d children: 30 mg/kg/d in 3 doses x 7-10 d © by author Pregnancy / breast feeding: ESCMID paromomycin Online / Humatin Lecture® Library 30 mg/kg/dLUMC in 3 coursedosis x 7d parasitology Outcomes of treatment - quick respons without sequelae - not effective (with or without persistent sequelae) - dose / compliance / resistence - temporary© by lactase author deficiency - post infectieus IBS ESCMID- bact Onlineerial overgrowth Lecture Library LUMC course parasitology “Bergen” outbreak • Bergen / Norway • Autumn 2004 • Drinking water contamination • N= 1262 • 2 years after giardiasis – Post-infectious fatigue 41%
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