by author Cystic Echinococcosis Rogelio López-Vélez MD, DTM&H, PhD National Referral Unit for Tropical Diseases Infectious Diseases Department
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1 Cystic Echinococcosis Rogelio López-Vélez MD, DTM&H, PhD National Referral Unit for Tropical Diseases Infectious Diseases Department Ramón y Cajal University Hospital. Madrid. Spain
2 National Referral Unit for Tropical Diseases. Infectious Diseases No disclosures
3 Echinococcosis Helminth, Cestod (tapeworm), genus Echinococcus E. granulosus: Cystic Echinococcosis (CE) E. multilocularis: Alveolar Echinococcosis (AE) E. vogeli; E. oligarthus: Policystic Echinococcosis (PCE) E. felidis, E. shiquicus Cystic Echinococcosis (CE) E.granulosus s.l. consists of five geno-species: E. granulosus s.s. (G1,G2,G3) E.equinus (G4) E.ortleppi (G5) E.canadensis (G6,G7,G8,G10) E.felidis Echinococcosis (Echinococcus spp.)
4 Cystic echinococcosis: Epidemiology CE is globally distributed and found in every continent except Antarctica. More than 1 million people are affected with echinococcosis at any one time In endemic regions, human incidence rates for CE can reach >50/ person-years, and prevalence levels as high as 5% 10% may occur in parts of Argentina, Chile, Uruguay, Peru, East Africa, Central Asia, Western China and Mediterranean region In slaughtered animals in some areas of South America varies from 20% 95% NTD, chronic and complex disease Is associated with poor hygiene in areas contiguous to sheep farming and dogs. Childhood acquisition is usual; however, clinical disease may become manifest only after many years.
5 800 cases/year Echinococcosis: Epidemiology in EU Rate: 0.2/
6 LIFE CYCLE of Echinococcus granulosus Dog/canid is the definitive hosts (the adult form lives in the small bowel) Sheep, goat, swine, cattle, horses, camel is the intermediate host (the larval form/cyst or metacestode lives in the tissues (mainly liver, lungs any viscera) The eggs can remain infective for months The liver and lungs are primarily affected, but any organ can be infected Human-to-human transmission does not occur The adult E granulosus (3-6 mm long) resides in the small bowel of the definitive hosts, dogs or other canids. Gravid proglottids release eggs that are passed in the feces. After ingestion by a suitable intermediate host (sheep, goat, swine, cattle, horses, camel), the egg hatches in the small bowel and releases an oncosphere that penetrates the intestinal wall and migrates through the circulatory system into various organs, especially the liver and lungs. In these organs, the oncosphere develops into a cyst that enlarges gradually, producing protoscolices and daughter cysts that fill the cyst interior. The definitive host becomes infected by ingesting the cyst-containing organs of the infected intermediate host. After ingestion, the protoscolices evaginate, attach to the intestinal mucosa, and develop into adult stages in 32 to 80 days.
7 Cysts (with the exception of bone) are composed of -PERICYST (host reactive tissue) -ENDOCYST (larva) -outer, acellular laminated layer -inner, germinal layer that gives rise to brood capsules >> protoscolices = pre adult -free daughter cysts (+/- laminar layer) in some stages -hydatid fluid, clear Hydatid cyst morphology -hydatid sand with abundant free-floating hooklets (when are degenerating)
8 PATHOLOGY of Echinococcus granulosus After ingestion of the eggs, the oncosphere hatches, penetrates the intestinal mucosa, and migrates through the bloodstream to internal organs (liver, lung, etc.) where a the cyst grows. The minimum time for development of protoscolices is 1 year. Each protoscolex is capable of generate into a new cyst (secondary echinococcosis) if the cystic fluid is spilled in a cavity such as the peritoneum The growth rate per year of the cyst is variable: 50%= 6-15 mm, 30%= 1-5 mm, 15%= no growth. Cysts range in size from few centimetres up to many litres (size can be related to the genotype) The majority of CE cases historically were attributed to G1. However, recent molecular studies of CE cases have revealed that G1 genotype is responsible for ~ 75% of human cases. Natural evolution: ACTIVE > <TRANSITIONAL > INACTIVE
9 May have different clinical manifestations, pathogenesis and drug sensitivity: G8 is predominantly pulmonary, grows slowly and few complications E.granulosus s.l. geno-species distribution
10 Incubation period is highly variable (up to >10 years) Clinical presentation depends of the organ involved, the location inside the organ, the surrounding structures, the size and integrity of the cyst It is not uncommon to be discovered incidentally Usually asymptomatic unless complications LOCATION Cystic echinococcosis: CLINICAL SYMPTOMS Single cyst in a single organ 40-80%. Also multiple sites Liver (right lobe) 70% abdominal pain, nausea and vomiting Lung 20% (lower lobes) chronic cough, chest pain and shortness of breath Other viscera 10% bones, kidneys, spleen, muscles, heart, mediastinum, brain, eyes
11 DIAGNOSIS of Cystic Echinococcosis: imaging Classification is based on ultrasonography on liver cysts but can be applied to any organ MRI>>CT: T2-sequences best detect liquid content, but miss wall calcifications CLASIFICATION Active: CE1, CE2 [CE3b] Transitional: CE3a, CE3b. Inactive: CE4, CE5 Long-term follow-up with imaging is required to evaluate the efficacy of treatment (recommended for 5 years)
12 Sonographic features of CE cysts WHO-IWGE, International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop 85: Double wall of the cyst, especially evident in fluid-filled CE1 cysts. Water lily sign of CE3a cysts, which reflects the detached endocyst fluctuating in the cyst fluid content. Honeycomb appearance of multivesiculated cysts (CE2 and CE3b), in which the impression of septa is formed by the adjacent walls of daughter vesicles (CE2) or in which daughter vesicles have formed in pseudosolid, hyperechoic, and nonhomogeneous cyst content (CE3b). The ball-of-wool sign of CE4 cysts, characterized by the appearance of hypoechoic, degenerating cyst membranes folded inside pseudo-solid cyst content. The wall calcification of cysts with pseudo-solid content (CE5).
13
14 DIAGNOSIS of Cystic Echinococcosis: serology Limited sensitivity (depend on the integrity of the wall and the stage of the cyst: false negative in early and late cysts) liver: 80-90% lung: 60-85% tests with recombinant antigens > sensitivity Xreactions: cysticercosis, fascioliasis, filariasis Sequential testing: 1st test (IHA, ELISA: Eg hydatid fluid antigen) followed by immunoblot with specific IgG subclases (Immunoblotting: 8KDa/12KDa subunits Eg antigen B) There is no test of cure, as serology results may remain positive for years even after successful treatment.
15 DIAGNOSIS of Cystic Echinococcosis: cytology Biopsies and punctures may also be performed for differential diagnosis of cysts from tumours and abscesses acellular laminated layer germinal layer protoescolices free hooklets Activity of the cysts is measured by: -integrity and motility of protoscolices -intact architecture of the germinal layer
16 CE in the liver: giant cysts
17 CE in the liver: multiple cysts Dr. Carmen-Michaela Cretu
18 CE in the liver: rupture into the biliary tree
19 CE in the liver: haemorrhage
20 CE in the liver: transdiafragmatic fistula
21 CE in the liver and in the lung
22 CE in the lungs Dr. Carmen-Michaela Cretu
23 Giant CE in the lung
24 CE in the lungs: rupture to pleural space
25 CE in the lungs: rupture to pleural space
26 CE in the lungs: lung abscess
27 Concomittant CE + TB
28 CE in the spleen
29 CE in the kidneys
30 CE in the psoas
31 Dissemniated CE: lungs + liver + peritoneal cavity
32 CE in the spine
33 CE in the spine
34 CE in the spine CMA
35 CE in the spine
36 CE in the spine: overinfected
37
38 CE in the pelvic gride
39 CE in the pelvic gride
40 CE in the shoulder
41 CE in the thoracic wall
42 CE in the leg muscles
43 Cardiac and endovascular CE
44 Cardiac and endovascular CE
45 Cava vein Pulmonary embolisms Liver R auricula
46 Cardiac and endovascular CE
47 endovascular CE: portal vein thrombosis
48 CE in the brain Neurol Med Chir (Tokyo) Aug;46(8):415-7.
49 There are 4 options for the treatment 1. Anti-infective drug treatment (albendazole) 2. Percutaneous puncture (PAIR) Percutaneous Puncture, Aspiration, Injection and Re-aspiration (PEVAC) Percutaneous Puncture large-bore needle and EVACuation 3. Surgery: Partial / total cystectomy 4. Watch and wait Cystic echinococcosis: TREATMENT The choice must primarily be based on the ultrasound images of the cyst, following a stage-specific approach, presence of complications and also on the medical infrastructure and human resources available.
50 Cystic echinococcosis: Albendazole treatment (1) Benzimidazole family Dose: mg/kg/day divided into 2 doses Take with fat-rich-meal (absorption increases 2-5 fold due to high lipid solubility) Entirely metabolized in the liver to albendazole sulfoxide Peak serum level at 2-5 hours; elimination half-life is 8-12 hours The overall efficacy of benzimidazoles has been overstated in the past. Works better in small (<6 cm) young active cysts: CE1, CE2 overall efficacy of 40-60% CE3b cysts respond initially (convert to CE4) but frequently relapse after treatment Repeated courses can be given
51 Cystic echinococcosis: Albendazole treatment (2) Length of treatment: 3-6 months, but In some cases with extensive/bone disease indefinite The process of cyst involution continues up to one year after termination of treatment Failure after initial response observed up to one year after termination of treatment For prevention of secondary CE after intervention: start 4 h before and up to 1 month after Praziquantel can be associated to prevent secondary CE based on its protoscolicidal activity The efficacy of adjunct nitazoxanide treatment remains to be defined Do not give when cysts are at risk of rupture (albendazole soften the pericystic tissue) Do not give in pregnancy Toxicity: >>liver enzymes (stop when go above 4 times NV); rare bone marrow suppression Follow up for a minimum of 5 years after treatment
52 Cystic echinococcosis Benznidazole treatment CE2 membrane detachment after albendazole treatment
53 Cystic echinococcosis Benznidazole treatment CE2 large cyst relapse after albendazole treatment
54 (PAIR) percutaneous Puncture, Aspiration, Injection and Re-aspiration Indicated for CE1, CE3a cysts of 5 to <10 cm Albendazole (4 h before until 1 month after). Puncture under US guidance. Aspiration (only hydatid fluid is removed). Cysto-biliary fistulas must be excluded (aspect of the fluid, test-strip for bilirrubine, injection of contrast). Aspiration of the contrast. Injection of 20% NaCl. Wait for min. Reaspiration. Follow-up for 5 years (PEVAC) Percutaneous Puncture large-bore needle and EVACuation Indicated for CE2, CE3b cysts Albendazole Cystic echinococcosis: PERCUTANEOUS TREATMENT Cysto-biliary fistulas must be excluded
55 20% hypertonic saline alcohol 96% and polidocanol 1% povidone iodine ethacrine lactate (rivanol) hydrogen peroxide silver nitrate cetrimide formalin Cystic echinococcosis PEVAC treatment
56 Cystic echinococcosis: surgery
57 Active cysts CE1 CE3a CE2 CE3b Early Rx Very late Rx 5-6 cm >5-6 cm <10 cm 10 cm Benzimidazoles (possibly higher efficacy) Benzimidazoles (possibly lower efficacy) PAIR Surgery / (continuous catheter drainage [CE1, CE3a], large-bore catheter [CE3a, CE3b, CE2 ]) Watch & wait Late Rx Risk of complications No Rx Stojkovic, Gottstein, Junghanss in: Manson s Tropical Diseases 2014 Inactive cysts CE4 CE5
58 Fistulas Cysto-biliary fistula: endoscopic retrograde cholangiopancreatography (ERCP) + ALBZ Cysto-bronchial fistula: surgery + ALBZ + antibiotics Bacterial infections Abscess: (blood-borne or retrograde via fistulas): drainage + antibiotics, followed by ALBZ (infection can sterilize the cyst) Compression Surgery Rupture Allergic reaction/anaphylactic shock: specific treatment Prevention of secondary CE: ALBZ +/- PZQ followed by surgery Embolism ALBZ +/- PZQ + surgery Rare locations TREATMENT OF COMPLICATED Cystic Echinococcosis Bone: ALBZ for life time?. Cardiac and endovascular (cava vein): surgery, do not give ALBZ (may precipitate rupture)
59 Cystic echinococcosis in the cava vein: surgery
60 Cystic echinococcosis in the cava vein: surgery
61 Cystic echinococcosis in the spine: surgery
62
63 Cystic echinococcosis: PAIR
64 Cystic echinococcosis in the spine: chronic osteomyelitis
65 Regular dog deworming with praziquantel Controlled slaughtering with meat inspection and appropriate disposal of infected organs (do not feed dogs with infected viscera) Vaccination of sheep with an E. granulosus recombinant antigen (EG95) Early detection of human cases (active screening campaigns with US) Public education campaigns Cystic echinococcosis: Control
66 Thanks for your attention
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