Worms and beyond in Southeast Asia

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Percival Allen
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1 Department of Epidemiology and Public Health Worms and beyond in Southeast Asia Peter Odermatt 8 March 2012

2 Einleitung

3 Vientiane, Laos Sethathirat Spital, May 2007 Patient Laotian (, 24 years), Migrant worker (Thailand) Reason: chronic diarrhoea (> 10 months) Several health centres consulted without improvemenet Observations Weak, pale, weight loss, dehydrated, amyotrophia, Patient report Watery stools (10-12 x /day) Abdominal pain Nausea and vomiting Weight loss > 12 kg Stool examination Giardia lamblia (cyst) Entamoeba histolytica (cyst) Trichomonas spp. Trichuris trichiura (whipworm) Oedema of lower extremities Temp.: 35.5 C, pulse: 90, Respiration: 24 / min.; blood pressure: 70/50 mmhg

4 Trichuriasis Endoscopy Rectal Prolapse

5 Vientiane, Laos Treatment Metronidazole, Ofloxacin Albendazole 400mg/day for 3 days Rehydration Seen again September 2007 Same symptoms as before Stool 3 stools examined Capillaria philippinensis Treatment Albendazole 400 mg/day for 30 days Control: full recovery

6 Intestinal Capillariasis Worm Length ~ 3.6 mm Worm Length ~ 2.6 mm C. philippinensis T. trichiura

7 Capillariasis Life cycle CDC, Atlanta Photo: T. Schuppisser

9 John Cross & Darwin Murrell

10 Intestinal Capillariasis 1962: first cases in Bacarra, Philippines (mysterious disease, intractable diarrhoea from Pudoc ) outbreaks in Philippines, Thailand: >1300 cases and 90 deaths Until today worldwide > 2000 cases + > 200 deaths, mainly in Southeast Asia Capillariasis: 1. Individuals clinician 2. Population (outbreak) public health 3. Traveller Travel Medicine

13 Food-borne trematodes (flukes) Tropism: = intestinal tract = lung = liver, bile duct

14 Pleurisy patient, Vientiane, Laos Boy, 14 years with chronic cough, chest pain (> 12 months), haemoptysis

16 Paratenic host Definitive host Adult worm Egg Metacercaria Second intermediate host Cercaria N. K. & Y. T. First intermediate host

19 Lungs: both sides affected Pleural effusion Pneumothorax Micro-cavity Calcifications Opacity Pre-treatment (n=13) 12/13 2/13 1/13 12/13 11/13 11/13 Post-treatment (6 months) (n=9) 8/9 1/9 0 8/9 7/9 9/9

20 Paragonimiasis: Parasite migration Cerebral paragonimiasis Pulmonary paragonimiasis Lung Pleural cavity Liver Cutaneous paragonimiasis Small intestine Skin Abdominal muscle

21 (Sleasak et al 2011)

22 Introduction into National Tuberculosis program (Sleasak et al 2011)

25 Liver flukes Clonorchis sinensis: China, Vietnam, Korea, Opisthorchis viverrini: Thailand, Laos, Opisthorchis felineus: Zentralasien 600 Mio. at risk, 67 Mio. infected

26 Opisthorchis viverrini: Adult Bile ducts Metacercarie Cyprinoid Fish: length: 5-10 cm Length ~ 10 mm

27 Distribution - Opisthorchis viverrini Infected: Thailand: 8 Mio Laos 2 Mio (5.5 Mio. at risk) (Sitthithaworn et al, 2011)

28 O. viverrini Prävalenz in Schulkindern Vientiane Saravane Provinz Saravane Distrikt (Pop ~80 000) (Rim et al 2003)

29 O. viverrini infection & risk factors in villages in Saravane district (n=814) Villages O. viverrini (%) Habit of eating raw fish (%) Never heard about O. viverrini (%) Availability and using of toilet at home (%) Kengsim NongMakyYang Napari Nabone Channeua Thamuongkao Khoksavath Nava Natum Leunbok Khokkao Km Benxeseth Total (Sayasone et al 2007)

30 O. viverrini infection prevalence (%) und intensity (eggs/gram stool) per age group < 6 y 6-15 y y y y y > 55 y % infected Intensity (epg) (Sayasone et al 2007)

31 O. viverrini infection prevalence (%) und intensity (eggs/gram stool) per age group and consumption of raw fish < 6 y 6-15 y y y y y > 55 y % infected % eating raw fish Intensity (epg) (Sayasone et al 2007)

32 Saravane: purgation of O. viverrini patients (n=97)

33 (Sayasone et al 2010)

34 (Forrer et al 2012)

35 (Forrer et al 2012)

36 (Sayasone et al 201?)

37 Current activities 1. Community-directed treatment and health education: shift responsibility from provincial to village level

39 Current activities 1. Community-directed treatment and health education: shift responsibility from provincial to village level 2. Effects of improved sanitation (latrine) utilisation on transmission of food-borne flukes 3. Integrated control: effects of treatment and health education combined with further preventive measures (environment: snails, fish cultivation, food preparation, etc) 4. Safety and efficacy of tribendimidine: potential alternative drug to praziquantel with larger spectrum (nematodes)

40 Opisthorchiasis: Clinical manifestation & consequences 1. Obstructive jaundice 2. Cholangitis 3. Cholecystitis 4. Gallstones 5. Hepatomegaly 6. Cholangiocarcinoma (CCA) (Sipra et al, 2007)

41 Cholangiocarcinoma (CCA) CCA is is a primary cancer originating in the biliary epithelium (cholangiocyte) 2 types of CCA: Intrahepatic duct Extrahepatic ducts 5-10% 60-70% 20-30% Sripa, 2005

42 Risk factors of CCA in Thailand Liver fluke Carcinogens Other factors Host immune: human leucocyste antigen (HLA) type, susceptibility gene, Xenobiotic metabolism Familial/genetic susceptibility Others: smoking, environment (Sripa and Pairojkul, 2008)

43 Cholangiocarcinoma (CCA) In Thailand: 1st rank of CCA in the world Northeast Thailand: 120 CCA per person/ yrs) 5000 new cases per year In Laos: CCA? (Sipra B et al, 2008)

44 2011 Laos, Saravane district Patient with Opisthorchis infection Age > 20 years n = 431

45 Hepatobiliary abnormalities in 431 O. viverrini infected patients Saravane, Laos Grade 0 Grade 1 Grade 2 Grade 3 Grade 0- normal parenchymal liver Grade 1- mild peridutal fibrosis Grade 2- moderate periductal fibrosis Grade 3- Advanced periductal fibrosis CCA Cirrhosis Fatty liver GBWT GBWI GBSL GBST BDD CBDD IHDS CCA- suspected cholangiocarcinoma GBWT- Gallbladder wall thickening GBWI- Gallbladder wall irregular GBSL- Gallbladder sludge GBST- Gallbladder stone(s) BDD- Bile duct dilated CBDD- Common bile duct dilated IHDS- Intrahepatic duct stone(s)

46 Suspected CCA case Key messages high prevalence of hepato-biliar morbidity 5 of 431 adult opisthorchiasis patient (= 1.2 %) with CCA suspected liver masses (Soukhathammavong Ayé et al 2011)

47 Next steps Cholangiocarcinoma (CCA) in Laos CCA versus other liver morbidity (cancers) CCA burden Risk factors: role of praziquantel treatment (repeated bile duct inflammations) CCA surveillance

48 Food transmitted helminths Nematodes capillariasis intestinal tract outbreak trichinellosis muscle outbreak gnathostomiasis any tissue small outbreaks Trematodes intestinal flukes intestinal tract areas (districts, ) paragonimiasis lung focal (villages) opisthorchiasis hepato-biliar areas (districts, ) CCA Cestodes cysticercosis any tissue areas (districts, )

49 Food transmitted helminths Nematodes capillariasis intestinal tract outbreak trichinellosis muscle outbreak gnathostomiasis any tissue small outbreaks Trematodes intestinal flukes intestinal tract areas (districts, ) paragonimiasis lung focal (villages) opisthorchiasis hepato-biliar areas (districts, ) CCA Cestodes cysticercosis any tissue areas (districts, ) epilepsy

50 Thank you

Presumptive Cancers Due to Agent Orange Exposure & Cholangiocarcinoma (Bile Duct - Liver Fluke Cancer)

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