Cystic Echinococcosis - ESCMID

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 ESCMID eLibrary

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National Referral Unit for Tropical Diseases. Infectious Diseases

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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.)

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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 >50/100 000person-years, and prevalence levels as high as 5%–10% may occur in parts ofArgentina, Chile, Uruguay, Peru, East Africa, Central Asia, Western China andMediterranean region

• In slaughtered animals in some areas of South America varies from 20%–95%

• NTD, chronic and complex disease

• Is associated with poor hygiene inareas contiguous to sheep farmingand dogs.

• Childhood acquisition is usual;however, clinical disease maybecome manifest only after manyyears.

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Rate: 0.2/100.000

Echinococcosis: Epidemiology in EU

≈800 cases/year

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LIFE CYCLE of Echinococcus granulosus

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.

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

Human-to-human

transmission

does not occur

The liver and lungs are

primarily affected, but any

organ can be infected

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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 sand with abundant free-floating hooklets (when are degenerating)

Hydatid cyst morphology

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• 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 thecyst grows. The minimum time for development of protoscolices is ≈1 year.

• Each protoscolex is capable of generate into a new cyst (secondary echinococcosis) ifthe 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 berelated 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

PATHOLOGY of Echinococcus granulosus

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E.granulosus s.l. geno-species distribution

May have different clinical manifestations, pathogenesis

and drug sensitivity: G8 is predominantly pulmonary,

grows slowly and few complications

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• 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

• 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…

Cystic echinococcosis: CLINICAL SYMPTOMS

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• 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)

DIAGNOSIS of Cystic Echinococcosis: imaging

.

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Sonographic features of CE cystsWHO-IWGE, 2003. International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings.

Acta Trop 85: 253–261

• 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 pseudo-

solid, 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).

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• 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.

DIAGNOSIS of Cystic Echinococcosis: serology

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• Biopsies and punctures may also be performed for differential

diagnosis of cysts from tumours and abscesses

– acellular laminated layer

– germinal layer

– protoescolices

– free hooklets

DIAGNOSIS of Cystic Echinococcosis: cytology

Activity of the cysts is measured by:

-integrity and motility of protoscolices

-intact architecture of the germinal layer

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CE in the liver: giant cysts

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CE in the liver: multiple cysts

Dr. Carmen-Michaela Cretu

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CE in the liver: rupture into the biliary tree

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CE in the liver: haemorrhage

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CE in the liver: transdiafragmatic fistula

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CE in the liver and in the lung

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CE in the lungs

Dr. Carmen-Michaela Cretu

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Giant CE in the lung

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CE in the lungs: rupture to pleural space

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CE in the lungs: rupture to pleural space

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CE in the lungs: lung abscess

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Concomittant CE + TB

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CE in the spleen

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CE in the kidneys

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CE in the psoas

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Dissemniated CE: lungs + liver + peritoneal cavity

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CE in the spine

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CE in the spine

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CMA

CE in the spine

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CE in the spine

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CE in the spine: overinfected

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CE in the pelvic gride

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CE in the pelvic gride

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CE in the shoulder

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CE in the thoracic wall

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CE in the leg muscles

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Cardiac and endovascular CE

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Cardiac and

endovascular CE

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Cava vein

R auricula

Liver

Pulmonary embolisms

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Cardiac and endovascular CE

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endovascular CE: portal vein thrombosis

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Neurol Med Chir (Tokyo). 2006 Aug;46(8):415-7.

CE in the brain

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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

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• Benzimidazole family

• Dose: 10–15 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

Cystic echinococcosis: Albendazole treatment (1)

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• 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

Cystic echinococcosis: Albendazole treatment (2)

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Cystic echinococcosisBenznidazole treatment

CE2 membrane detachment after albendazole treatment ESCMID eLibrary

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Cystic echinococcosis

Benznidazole treatment

CE2 large cyst relapse after albendazole treatment

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(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 mustbe excluded (aspect of the fluid, test-strip for bilirrubine, injection of contrast). Aspiration of thecontrast. Injection of 20% NaCl. Wait for 15-20 min. Reaspiration.

• Follow-up for 5 years

(PEVAC) Percutaneous Puncture large-bore needle and EVACuation• Indicated for CE2, CE3b cysts

• Albendazole

• Cysto-biliary fistulas must be excluded

Cystic echinococcosis: PERCUTANEOUS TREATMENT

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– 20% hypertonic saline– alcohol 96% and polidocanol 1%– povidone iodine– ethacrine lactate (rivanol)– hydrogen peroxide– silver nitrate– cetrimide– formalin

Cystic echinococcosis

PEVAC treatment

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Cystic echinococcosis: surgery

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CE1

CE3a

CE4

CE5

CE2

CE3b

≤5-6 cm >5-6 cm <10 cm ≥10 cm

Early Rx Very late RxActive

cystsInactive

cysts

Benzimidazoles (possibly higher efficacy)

Benzimidazoles (possibly lower efficacy)

PAIR

Surgery / (continuous catheter drainage [CE1, CE3a],

large-bore catheter [CE3a, CE3b, CE2 ])

Watch & wait

No Rx

Risk of complications

Late Rx

Stojkovic, Gottstein, Junghanss

in: Manson‘s Tropical Diseases

2014

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• 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– Bone: ALBZ for life time?

– Cardiac and endovascular (cava vein): surgery, do not give ALBZ (may precipitate rupture)

TREATMENT OF COMPLICATED Cystic Echinococcosis

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Cystic echinococcosis in the cava vein: surgery

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Cystic echinococcosis in the cava vein: surgery

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Cystic echinococcosis in the spine: surgery

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Cystic echinococcosis: PAIR

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Cystic echinococcosis in the spine: chronic osteomyelitis

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• 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

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Thanks for your attention

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