HYDATID DISEASES

ByDr. Sayan Chakraborty

2nd Year PGT- MD Tropical MedicineSchool of Tropical Medicine, Kolkata

E-mail: dr.sayan@gmail.com

WHO/CDC NTDs

CASE HISTORY An 26 yrs old female presented with dull pain right side

of upper abdomen, a dragging sensation over right hypochondrium and occasional fever nearly one month

• Pain not relieved with analgesics

• Examination revealed mild hepatomegaly

• Routine blood test was normal

• Advised for imaging study of abdomen

DIFFERENTIAL DIAGNOSISHEPATIC SAPCE OCCUPYING LESIONS

Cystic/PseudocysticSpace-Occupying Lesionswith Liquid Content

Solid Space-OccupyingLesions

CONGENITAL SPACE-OCCUPYING LESIONS

Simple cyst Haemorrhagic simple cyst

VASCULAR SPACE-OCCUPYING LESIONS

Haematoma HaematomaHaemangioma

INFECTIOUS SPACE-OCCUPYING LESIONS

CE [CE1, CE2, CE3a,CE3b (mixed cystic-solid)]AE with pseudocystAbscess

CE [CE3b (mixed cystic-solid),CE4 and CE5]AETuberculoma

BENIGN SPACE-OCCUPYING LESIONS

Cystadenoma Hepatic adenomaFocal nodular hyperplasia

MALIGNANT SPACE-OCCUPYING LESIONS

CystadenocarcinomaLiver metastases with central necrosis

Metastatic liver tumoursHepatocellular carcinomaCholangiocarcinoma

INTRODUCTION• Zoonosis• 3 forms of Echinococcosis:Cystic echinococcosis (CE): Tropical and subtropical regions;

Echinococcus granulosus (Unilocular cyst) Alveolar echinococcosis (AE): Temperate northern

hemisphere; Echinococcus multilocularis (Multilocular cyst)Polycystic echinococcosis (PE): Latin America; Echinococcus

vogeli & Echinococcus oligarthus

CE eradicated in Iceland, New Zealand and Tasmania. Definitive host: Dogs and other canines Intermediate host: Sheep, goat, swine etc

GLOBAL DISTRIBUTION

Figure 1. Geographic distribution of hydatid disease. Map shows areas in which hydatid disease is endemic due to the transmission of E granulosus by means of the dog-sheep cycle (solid red areas). Red stripes indicate areas where transmission occurs by means of alternative life cycles in which carnivores such as wolves and foxes serve as definitive hosts and goats, camels, and horses serve as intermediate hosts. Transmission by means of alternative life cycles is common in North Africa, the Middle and Far East, the United States, Canada, and Iceland

LIFE CYCLE

EPIDEMIOLOGY Cystic Echinococcosis:• Highly endemic in pastoral communities• Genotypes G1–10; G1 strain of E. granulosus accounts for 95%

of human infections and has a dog-sheep transmission• Incidence rates as high as 50/100 000 person-years• Risk factors: Ownership of livestock (mainly dogs, sheep);

occupation (pastoralism, agriculture); uncontrolled slaughtering; poor water hygiene Alveolar Echinococcosis: • Definitive hosts: mainly foxes and domestic dogs• Intermediate hosts: Arvicolid and Cricetid rodents• Prevalence: 0.02% and 1.4%• Global annual incidence 18,235 cases per year

CYSTICECHINOCOCCOSIS

PATHOGENESIS• One or more spherical cysts, most frequently in liver & lungs• Tissue damage & organ dysfunction by gradual process of

space occupying compression• Cyst structure:o Outer pericyst: composed of modified host cells that form a

dense and fibrous protective zoneo Middle laminated membrane: acellular and allows the passage

of nutriento Inner germinal layer: forms brood capsule which develops

asexually into protoscolices (the larval stage of the parasite) from which daughter cysts are produced.

• Cysts modulate immune response by Th1 cell activation & impairment of macrophages

Natural Evolution of Cysts

CLINICAL FEATURES• Asymptomatic in most cases; incidental finding• Most symptomatic cysts are ≥ 5 cm• Pressure effect on liver and biliary tree• Abdominal pain , hepatomegaly, jaundice

• Pulmonary cysts: Cough with expectoration, SOB, chest pain, hemoptysis• Other sites: Pathological #, Brain SOL, Conduction

defects, Pericarditis, Pelvic mass• Leakage of cyst contents or infection of cyst• Pain, flushing and urticaria• Anaphylactic reaction• Fever and sepsis

COMPLICATION OF CYSTS• Cysts with fistulas• Biliary/bronchial obstruction (due to spillage of cyst content via cysto-biliary/cysto-bronchial fistulas)• Bacterial infection• Compression syndromesBlood vessels (leading to thrombosis, Budd–Chiari

syndrome)Biliary ductsBronchiParenchyma/muscles, nerves (leading to atrophy)• Cyst rupture• Venous/arterial embolism

OTHER DDx

• Neurocysticercosis• Cholangiocarcinoma • Imaging in NonSmall Cell Lung Cancer• Imaging in Small Cell Lung Cancer• Imaging of Benign Breast Calcifications• Lung Metastases Imaging• Metastatic Cancer With Unknown Primary Site• Pancreatic Pseudocyst Imaging• Pyonephrosis• Renal Cancer• Splenic Abscess

INVESTIGATIONS LABORATORY WORK UP:• Routine lab tests: No specific findings• Cyst rupture in biliary tree: marked & transient elevation of

cholestatic enzyme levels , often with hyperamylasemia and eosinophilia <15% (in 60% cases)

• SEROLOGY: Confirmatory role; Indirect hemagglutination test & ELISA for detection of anti-Echinococcus Antibodies [IgG]

• 10% hepatic cysts & 40% pulmonary cysts exhibit false negative results

-ve in CE1/CE2/CE4/CE5; +ve only when endocyst ruptures• Diagnostic puncture & aspiration can be performed for

histological diagnosis• PCR contribute to the differential diagnosis between CE and

AE in doubt.

INVESTIGATIONS IMAGING: USG is Inv of choice (Gharbi US classification of

1981 & WHO-IWGE 2003 classification)

OTHER INVESTIGATIONS• CT scan can detect extrahepatic smaller cysts, differentiating

parasitic from nonparasitic by measurement of cyst density & for follow up studies during chemotherapy

• MRI used in the evaluation of postsurgical residual lesions, recurrences & cardiac infections. Also superior in identifying changes of the intrahepatic and extrahepatic venous system & in identifying cystobiliary fistulas.

• Assessment of Parasite Viability: Histopathology (intact parasite-derived cyst wall including

germinal layer) Evaluation of the protoscolices (flame cell activity and

morphological integrity; eosin staining) Metabolic viability assessment using high-field H-MRS of cyst

content RT-PCR

CASONI’S TEST

MANAGEMENT Depends on the size, location and manifestations of cysts In uncomplicated cysts: “Expert consensus for the diagnosis

and treatment of cystic and alveolar echinococcosis in humans”, published by the WHO-Informal Working Group on Echinococcosis recommends four treatment modalities:

• 1. Drug treatment with benzimidazoles• 2. Percutaneous sterilization techniques• 3. Surgery• 4. ‘Watch and wait’

BENZIMIDAZOLES Indication: 1. CE 1,2,3a,3b of size 5-6 cm2. Prevention of secondary CE after interventions or after

spontaneous rupture; starting at least 4 hours before & upto 1 month after intervention

• Dosage: Albendazole 10-15 mg/kg/day in 2 divided doses or Mebendazole 40-50 mg/kg/day in 3 divided doses; with a fat-rich meal for 3-6 months

• Monitoring: Liver enzymes (upto 2-4x) & CBC at day 5, 10, then at 2 weekly intervals ,later monthly

• Contraindications: Pregnancy; cysts at risk of rupture; hepatoxicity; leucopenia; bone marrow suppression

• Follow up: 12 months after treatment completion to look for re-activation & min of 5 yrs after cysts reached inactive stage (CE4, CE5)

Puncture – Aspiration – Injection – Re-Aspiration (PAIR)

• Indication: CE1 and CE3a cysts of liver of size 5–6 to <10 cm• Principle: Sterilization of the germinal layer and protoscolices.

Only fluid is removed; all other parasitic material remains • Prerequisites: Experienced interventionalist; resuscitation set

up for severe anaphylactic reactions & surgical back-up

Puncture – Aspiration – Injection – Re-Aspiration (PAIR)

• Major steps :1. Prophylaxis of secondary echinococcosis with albendazole2. Percutaneous puncture of the cyst under US (or CT) guidance3. Aspiration of cyst fluid4. Testing for bilirubin (evaluation of aspect of fluid and test strip result) and injection of contrast medium (verification of absence of cysto-biliary communications)5. Aspiration of contrast medium6. If fistulas are reliably ruled out: injection of protoscolicidal agent – 95% ethanol or 20% NaCl to remain in the cyst for 10–15 mins7. Re-aspiration of the fluid8. Follow-up for a minimum of 5 years to detect relapses and secondary CE

SURGERY

• INDICATION:1. Any cyst >10 cm

irrespective of CE staging2. Cysts 5-6 to <10 cm in CE 2

and CE 3b3. Complicated cysts

• FOLLOW-UP: minimum of 5 years.

SURGERY1. Partial Cystectomy: Removal of the parasite-derived cyst components (endocyst) & part of the pericyst (host-derived connective tissue capsule).2. Total cystectomy and Resectiona. Total cystectomy: endocyst and the entire pericystb. Resection: additional removal of part of the organ where CE-cyst is embedded

‘Watch and Wait’

• Cyst allowed to progress along its natural course if asymptomatic

• Indicated in CE 4 & CE 5 Stages

• Follow-up patients with CE4 and CE5 cysts for a min of 5 years

Management of Complicated Cyst

Cysto-biliary and cysto-bronchial fistulas: ERCP, if possible, followed by early surgery under albendazole cover

Bacterial Infection: Initially, abscess management with drainage and antibiotics followed by specific management of residual CE cyst/cavity & albendazole therapy

Compression Syndromes: Rapid decompression of blood vessels, bile ducts, bronchi, parenchyma, muscle, nerves

Cyst Rupture: Allergic Reactions and Secondary CE:• standard approach to allergic reactions including anaphylactic

shock followed by CE-specific treatment• To prevent secondary CE, surgical intervention to clear CE cyst

material and benzimidazole therapy

PREVENTION 4 phases: (1) planning; (2) attack; (3) consolidation; and (4)

maintenance of eradication

Horizontal approaches: Slow-track (>25 yrs)• reduction of disease transmission through primary healthcare

interventions, including health education, general husbandry improvements, upgrading of abattoirs & meat inspection

• regular deworming of dogs by their owners

Vertical or fast-track approach: 3-5 yrs• Mass treatment of dogs, dog registration and reduction of

stray dog numbers• EG95 vaccine 95% effective against ovine hydatidosis

ALVEOLARECHINOCOCCOSIS

INTRODUCTION Organism: Echinococcus multilocularis Global distribution: Temperate northern hemisphere Epidemiology: • Definitive hosts: mainly foxes and domestic dogs• Intermediate hosts: Arvicolid and Cricetid rodents• Prevalence: 0.02% and 1.4%• Global annual incidence: 18,235 cases per year Site of infection:• E. multilocularis metacestode (larva) develops primarily in the

liver. • In advanced stages, other sites may become metastasized

such as retroperitoneum, lungs, brain and bones

PATHOLOGY• Conglomerate of scattered vesicles, each ranging from a few

mm to cm in size• Germinal layer represents the proliferating metacestode

generating new vesicles, which leads to the tumour-like behaviour of the parasite.

• A granulomatous host reaction surrounds the metacestode, including a vigorous synthesis of fibrous and germinative tissue.

• 3 immune mediated clinical outcome:(1) resistance as shown by the presence of ‘dying out’ or ‘aborted’ metacestodes; (2) controlled susceptibility by a slowly growing metacestode tissue – presents 5–15 years after infection;(3) Uncontrolled hyperproliferation of the metacestode due to an impaired immune response

DIAGNOSIS• Serology: Em2, Em2+, Em18 antigens• Imaging: USG/CT/MRI/PET• Diagnostic puncture and aspiration of parasitic material• Histology• RT-PCR

• PNM Classification: Resemblance to malignant diseasesP primary mass in the liverN involvement of neighbouring organs (lymph nodes)M metastases

MANAGEMENT• Curative treatment is possible with combination of radical

surgery with 2 cm liver margin & subsequent drug treatment (benzimidazoles) for at least 2 years.

• Life long follow up• Recurrences have been observed almost 20 years after surgery• After successful surgery, anti-Em18 or anti-Em2+ antibodies

decline rapidly, and seroconversion to undetectable levels correlates well with curative resection

• Advanced stage lesions: life long benzimidazole therapy & management of acute problems such as obstruction of bile ducts, abscess formation and thrombosis of major blood vessels

• Liver transplantation

ATYPICAL CASES

PUBLICATIONS

PUBLICATIONS

PUBLICATIONS

HYDATID CYST OF BRAIN

HYDATID CYST OF BONE

HYDATID CYST OF SEMINAL VESICLE

HYDATID CYST OF SPINE

REFERENCES1. Manson’s Tropical Diseases (23rd Ed)2. Harrison’s Principles of Internal Medicine 19th edition3. Mandell Douglas and Bennett Principles and Practice of

Infectious Diseases 7th Edition 4. WHO | Echinococcosis; www.who.int/echinococcosis/en/5. CDC – Echinococcosis;

www.cdc.gov/parasites/echinococcosis/6. Links:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3716240/ http://europepmc.org/abstract/med/593481 http://pmj.bmj.com/content/79/928/113.full