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Etiology
Global zoonotic disease
DISEASES CAUSED BY FLUKES IN THE BILE DUCT


               Clonorchiasis                    Opisthorchiasis           Fascioliasis
Parasite       Clonorchis sinensis              Opisthorchis felineus     Fasciola hepatica
Other          Dogs, cats, pigs                 Dogs, cats, foxes, pigs   Sheep, cattle
mammalian
hosts
Mode of        Ova in faeces, water             As for C. sinensis        Ova in faeces on to wet pasture
spread
1st intermed   Snails                           Snails                    Snails
host
2nd intermed   Freshwater fish                  Freshwater fish           Encysts on vegetation
host
Geographical   Far East, especially South       Far East, especially      Cosmopolitan, including UK
distribution   China                            North-east Thailand
Pathology      E. coli cholangitis,             As for C. sinensis        Toxaemia, cholangitis, eosinophilia
               abscesses, biliary
               carcinoma
Symptoms       Often symptom-free,              As for C. sinensis        Unexplained fever, tender liver, may be
               recurrent jaundice                                         ectopic, e.g. subcutaneous fluke
Diagnosis      Ova in stool or duodenal         As for C. sinensis        As for C. sinensis, also serology
               aspirate
Prevention     Cook fish                        Cook fish                 Avoid contaminated watercress
Treatment      Praziquantel 25 mg/kg 8-         As for C. sinensis but    Triclabendazole 10 mg/kg single dose;
               hourly for 2 days                for 1 day only            repeat treatment may be required
 Most of the areas with high endemicity of human fascioliasis
  involve F.hepatica.

 In Africa F. gigantica predominates.

 In Asia / Egypt: F. hepatica / F. gigantica overlaps & difficult to
  identify the particular species involved, so referred to as Fasciola
  species
 Infective stage

 Excystation


 Migration




 Diagnostic stage
Clinical concept   Epidemiological concept
• Fasciola species inhabit the
 hepatobiliary system causing
  considerable human
  morbidity dependent on the
  number of worms & stage of
  infection
• The course of infection passes through three phases:
   • The acute phase
   • The chronic phase
   • The obstructive phase

• Pathology / clinical manifestations are related to the phase
The acute phase:
 Coincides with migration
  of the immature flukes
  through the peritoneal
  cavity, penetrating liver
  capsule then through
 liver parenchyma till they   liver
  reach the bile ducts.
 The acute phase:                 adult
 It persists for several weeks
  to months (3-4 months)

 Severe pathology results
  from parasite migration
      / destruction
  of parenchymal tissue,
  causing
  toxic and allergic
  reactions                       liver
The acute phase
    Symptoms :
                            • Acute dyspepsia
                            • Prolonged high fever
                            • Hepatomegaly/
  Acute symptoms           abdominal pain in the
                            right hypochondrium
 Asymptomatic (unusual)
                            •Urticaria
 Severe illness
                            •Peripheral
 (prostration & jaundice)   eosinophilia,   up   to
   (unusual)                80%
                            •Anaemia
 The chronic phase,
  coincides with the
  presence of the
  flukes in the bile
  ducts
 The life span of the
  parasite is 10-13
  years
 Pathology tends to
  be mild
The chronic phase Symptoms :
•    Asymptomatic

     Recurrent cholangitis
     Few GIT symptoms:
    Intermittent fever with persistent
    prominent eosinophilia
    Recurrences of the acute signs &
    symptoms
The chronic phase:
  Obstructive phase
 (heavy / prolonged
  infection)
 Coincides with epithelial
  changes in the bile ducts
  due to irritation of the
  epithelium by the spines &
  the activity of proline
  enzyme produced bt the
  worm
 The chronic phase:
                              adults
  Obstructive phase
 Severe pathology occur
  in the form of epithelial
  hyperplasia &
  proliferation, periductal
       inflammation
    then fibrosis &even
  calcification leading to
  partial obstruction
 Symptoms
 Recurrent cholangitis &
  cholecystitis (calculous
  or acalculous)
Ectopic fascioliasis may occur during any of the three phases of
the disease but is most common during the acute phase
1. Juveniles that migrate out of the intestine but do not locate in
the liver so they form ectopic lesions in many abdominal
tissues

2.Juveniles that enter the portal circulation, so distributed
throughout the body .
   Manifested as masses, abscesses, migration tracks or
    haemorrage.
   These are often misdiagnosed as malignant ulcers or
    tumours .
   Exploratory abdominal surgery may be needed to make the
    diagnosis
Interesting ectopic sites & lesions
   Gastric fascioliasis
   Fascioliasis of the head of pancreas
   A mass in the right iliac fossa
   The peritoneal cavity        massive ascitis
   Mitral insufficiency secondary to myocardial fibrosis
   intraocular bleeding
   Hydrocele due to epididymitis
    Effusion of the knee joint
   Ectopic Fasciola worms in the ankle joint
   Cervical / generalized lymphadenopathy
   Abdominal subcutaneous nodules
   Pleural effusion associated with/without pulmonary
    infiltrates, pyopneumothorax & pleurisy .
1.   Liver abscess & haematoma (subcapsular) (acute stage)
2.   Obstructive jaundice : Obstruction of CBD by Fasciola adults.
3.   Biliary sludge / stones: in gall bladder & biliary tree may be
     formed in chronic patients, which remains unchanged after
     therapy may predispose to recurrent cholecystitis, cholangitis or
     biliary stone
4. Biliary cirrhosis :due to the peri-ductal fibrosis
5. Bleeding : Bleeding may occur due to ulcerations in the
     common bile duct (haemobilia)
6. Death: rare, major causes of death are biliary bleeding &
     biliary cirrhosis
Diagnosis
 1. Clinical + Haematological
  /biochemical findings
 2. Parasitological diagnosis
 3. Immuno-diagnosis                    1
 4. Imaging procedures          2               3
 5. Liver biopsy


                                     4       5
Clinical + the haematological / biochemical
               Not reliable because:
• The clinical manifestations are not markedly different from
   hepatobiliary disease of other origins.
  so hepatomegaly, fever, anaemia , marked eosinophilia are
   only highly suggestive of the disease but not specific.
• Ectopic localization of the parasite may cause a confusing
   clinical presentation
2. Parasitological diagnosis not
   accurate because:
- Eggs are not excreted during the
   invasive stage of infection when
   many patients present with severe
   symptoms
- Sometimes eggs are undetectable
   during the chronic phase.
- Differentiation of eggs of F. hepatica,
   F. gigantica, echinostomes &
   Fasciolopsis is difficult
3. Immunodiagnosis:
  The advantage over parasitological techniques is:
  Can detect early, prepatent infections & chronic stage with little or
                               no egg output.
  Tests have been developed for
•    Detection of Fasciola antigens (Circulating, Coproantigens)
•    Detection of the circulating antibodies (IgM, IgG, IgG4)
•    Detection of the circulating immune complexes.
Numerous assays for immunodiagnosis:
• ELISA
• Indirect haemagglutination test (IHA)
• Counter immuno electrophoresis (CIEP)
• Indirect fluorescent antibody test (IFA)

reveale 100% sensitivity & specificity e.g. IgG4 ELISA (recombinant
  CL-1) & cystatin capture ELISA (cysteine proteinase)
4.   Imaging
Various imaging techniques proved useful to diagnose human
  fascioliasis
 1. Ultrasonography (US)
 2. Computed Axial Tomography(CAT)
 3. Magnetic Resonance Imaging (MRI)
 4. Endoscopic Retrograde Cholangio-Pancreatography
  (E.R.C.P.)
 5. Percutaneous transhepatic cholangiographv (P.T.C)
Valuable in the diagnosis of…
 The migratory tracks          CT
 of the juvenile flukes
  seen as peripherally
  located branching or
  tortuous lesions
 Pathological lesions
  secondary to migration
  e.g. abscesses &
  parenchymal
  hemorrhages
sonar
 Vermiform flukes
  moving within the gall
  bladder
 Hepatomegaly &
  periportal fibrosis


 Bile aspiration from
 the gall bladder for
 verification in cases
 suspicious to be
 metastatic liver
 disease (US, E.R.C.P)
5. Liver biopsy may
 demonstrate:

• Microabscesses
                           liver
• Tunnels of parenchymal
necrosis
• Eggs & adult worms
                                   adult
• Chemotherapeutic agents in common use in human fascioliasis:
 Effective with no or little side effects: Triclabendazole, bithionol,
  Mirazid
 Effective with side effects: severe (dehydroementine), or
  moderate (Metronidazole)
 Controversial therapeutic results (Praziquantel)
Triclabendazole TCZ appears to be the drug of choice for acute &
  chronic human fascioliasis, recently registered for human use
  against fascioliasis (WHO, 1998):
 Effective against juveniles / adults
 Excellent tolerance &efficacy in adults &children
 Ease of administration (single oral dose)
The criteria for cure :
1) Amelioration of symptoms & achievement of clinical
   wellbeing (Clinical cure)
2) Normalization of haematological & biochemical data:
   declining then returning to normal values
3) Absence of ova (parasitologic cure) in repeated stool
   examinations in chronic cases
4) Decreasing antigenaemia / antibody levels
5) Disappearance or improvement of imaging findings
Treatment efficacy
• The detection of circulating Fasciola antigen & coproantigen is an
  efficient immuno-diagnostic tool to assess the effect of therapy in
  fascioliasis, as antigenaemia in the host reflects an active infection
• Role of antibody detection to assess treatment efficacy is
  controversial.
• Individuals who do not
  respond to oral drug
  therapy can be treated
  successfully by biliary
  drainage & the take out of
  worms or by flushing of
  the biliary system with
  povidone iodide
The epidemiological picture of the disease
       has changed in recent years.
There is a significant
positive association
between human
fascioliasis &
schistosomiasis mansoni
Snail intermediate   host
Reservoir hosts
1.   Periodic examination /
     treatment of livestock
2.   Control of the snail vectors
3.   Health education.
4.   People must be aware of how
     infection might occur.

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Fasciolaosis for 3rd

  • 1.
  • 3. DISEASES CAUSED BY FLUKES IN THE BILE DUCT Clonorchiasis Opisthorchiasis Fascioliasis Parasite Clonorchis sinensis Opisthorchis felineus Fasciola hepatica Other Dogs, cats, pigs Dogs, cats, foxes, pigs Sheep, cattle mammalian hosts Mode of Ova in faeces, water As for C. sinensis Ova in faeces on to wet pasture spread 1st intermed Snails Snails Snails host 2nd intermed Freshwater fish Freshwater fish Encysts on vegetation host Geographical Far East, especially South Far East, especially Cosmopolitan, including UK distribution China North-east Thailand Pathology E. coli cholangitis, As for C. sinensis Toxaemia, cholangitis, eosinophilia abscesses, biliary carcinoma Symptoms Often symptom-free, As for C. sinensis Unexplained fever, tender liver, may be recurrent jaundice ectopic, e.g. subcutaneous fluke Diagnosis Ova in stool or duodenal As for C. sinensis As for C. sinensis, also serology aspirate Prevention Cook fish Cook fish Avoid contaminated watercress Treatment Praziquantel 25 mg/kg 8- As for C. sinensis but Triclabendazole 10 mg/kg single dose; hourly for 2 days for 1 day only repeat treatment may be required
  • 4.  Most of the areas with high endemicity of human fascioliasis involve F.hepatica.  In Africa F. gigantica predominates.  In Asia / Egypt: F. hepatica / F. gigantica overlaps & difficult to identify the particular species involved, so referred to as Fasciola species
  • 5.  Infective stage  Excystation  Migration  Diagnostic stage
  • 6. Clinical concept Epidemiological concept
  • 7. • Fasciola species inhabit the hepatobiliary system causing considerable human morbidity dependent on the number of worms & stage of infection
  • 8. • The course of infection passes through three phases: • The acute phase • The chronic phase • The obstructive phase • Pathology / clinical manifestations are related to the phase
  • 9. The acute phase:  Coincides with migration of the immature flukes through the peritoneal cavity, penetrating liver capsule then through liver parenchyma till they liver reach the bile ducts.
  • 10.  The acute phase: adult  It persists for several weeks to months (3-4 months)  Severe pathology results from parasite migration / destruction of parenchymal tissue, causing toxic and allergic reactions liver
  • 11. The acute phase Symptoms : • Acute dyspepsia • Prolonged high fever • Hepatomegaly/  Acute symptoms abdominal pain in the right hypochondrium  Asymptomatic (unusual) •Urticaria  Severe illness •Peripheral (prostration & jaundice) eosinophilia, up to (unusual) 80% •Anaemia
  • 12.  The chronic phase, coincides with the presence of the flukes in the bile ducts  The life span of the parasite is 10-13 years  Pathology tends to be mild
  • 13. The chronic phase Symptoms : • Asymptomatic Recurrent cholangitis Few GIT symptoms: Intermittent fever with persistent prominent eosinophilia Recurrences of the acute signs & symptoms
  • 14. The chronic phase: Obstructive phase  (heavy / prolonged infection)  Coincides with epithelial changes in the bile ducts due to irritation of the epithelium by the spines & the activity of proline enzyme produced bt the worm
  • 15.  The chronic phase: adults Obstructive phase  Severe pathology occur in the form of epithelial hyperplasia & proliferation, periductal inflammation then fibrosis &even calcification leading to partial obstruction  Symptoms Recurrent cholangitis & cholecystitis (calculous or acalculous)
  • 16. Ectopic fascioliasis may occur during any of the three phases of the disease but is most common during the acute phase 1. Juveniles that migrate out of the intestine but do not locate in the liver so they form ectopic lesions in many abdominal tissues 2.Juveniles that enter the portal circulation, so distributed throughout the body .  Manifested as masses, abscesses, migration tracks or haemorrage.  These are often misdiagnosed as malignant ulcers or tumours .  Exploratory abdominal surgery may be needed to make the diagnosis
  • 17. Interesting ectopic sites & lesions  Gastric fascioliasis  Fascioliasis of the head of pancreas  A mass in the right iliac fossa  The peritoneal cavity massive ascitis  Mitral insufficiency secondary to myocardial fibrosis  intraocular bleeding  Hydrocele due to epididymitis  Effusion of the knee joint  Ectopic Fasciola worms in the ankle joint  Cervical / generalized lymphadenopathy  Abdominal subcutaneous nodules  Pleural effusion associated with/without pulmonary infiltrates, pyopneumothorax & pleurisy .
  • 18. 1. Liver abscess & haematoma (subcapsular) (acute stage) 2. Obstructive jaundice : Obstruction of CBD by Fasciola adults. 3. Biliary sludge / stones: in gall bladder & biliary tree may be formed in chronic patients, which remains unchanged after therapy may predispose to recurrent cholecystitis, cholangitis or biliary stone 4. Biliary cirrhosis :due to the peri-ductal fibrosis 5. Bleeding : Bleeding may occur due to ulcerations in the common bile duct (haemobilia) 6. Death: rare, major causes of death are biliary bleeding & biliary cirrhosis
  • 19. Diagnosis  1. Clinical + Haematological /biochemical findings  2. Parasitological diagnosis  3. Immuno-diagnosis 1  4. Imaging procedures 2 3  5. Liver biopsy 4 5
  • 20. Clinical + the haematological / biochemical Not reliable because: • The clinical manifestations are not markedly different from hepatobiliary disease of other origins. so hepatomegaly, fever, anaemia , marked eosinophilia are only highly suggestive of the disease but not specific. • Ectopic localization of the parasite may cause a confusing clinical presentation
  • 21. 2. Parasitological diagnosis not accurate because: - Eggs are not excreted during the invasive stage of infection when many patients present with severe symptoms - Sometimes eggs are undetectable during the chronic phase. - Differentiation of eggs of F. hepatica, F. gigantica, echinostomes & Fasciolopsis is difficult
  • 22. 3. Immunodiagnosis: The advantage over parasitological techniques is: Can detect early, prepatent infections & chronic stage with little or no egg output. Tests have been developed for • Detection of Fasciola antigens (Circulating, Coproantigens) • Detection of the circulating antibodies (IgM, IgG, IgG4) • Detection of the circulating immune complexes.
  • 23. Numerous assays for immunodiagnosis: • ELISA • Indirect haemagglutination test (IHA) • Counter immuno electrophoresis (CIEP) • Indirect fluorescent antibody test (IFA) reveale 100% sensitivity & specificity e.g. IgG4 ELISA (recombinant CL-1) & cystatin capture ELISA (cysteine proteinase)
  • 24. 4. Imaging Various imaging techniques proved useful to diagnose human fascioliasis  1. Ultrasonography (US)  2. Computed Axial Tomography(CAT)  3. Magnetic Resonance Imaging (MRI)  4. Endoscopic Retrograde Cholangio-Pancreatography (E.R.C.P.)  5. Percutaneous transhepatic cholangiographv (P.T.C)
  • 25. Valuable in the diagnosis of…  The migratory tracks CT of the juvenile flukes seen as peripherally located branching or tortuous lesions  Pathological lesions secondary to migration e.g. abscesses & parenchymal hemorrhages
  • 26. sonar  Vermiform flukes moving within the gall bladder
  • 27.  Hepatomegaly & periportal fibrosis  Bile aspiration from the gall bladder for verification in cases suspicious to be metastatic liver disease (US, E.R.C.P)
  • 28. 5. Liver biopsy may demonstrate: • Microabscesses liver • Tunnels of parenchymal necrosis • Eggs & adult worms adult
  • 29. • Chemotherapeutic agents in common use in human fascioliasis:  Effective with no or little side effects: Triclabendazole, bithionol, Mirazid  Effective with side effects: severe (dehydroementine), or moderate (Metronidazole)  Controversial therapeutic results (Praziquantel)
  • 30. Triclabendazole TCZ appears to be the drug of choice for acute & chronic human fascioliasis, recently registered for human use against fascioliasis (WHO, 1998):  Effective against juveniles / adults  Excellent tolerance &efficacy in adults &children  Ease of administration (single oral dose)
  • 31. The criteria for cure : 1) Amelioration of symptoms & achievement of clinical wellbeing (Clinical cure) 2) Normalization of haematological & biochemical data: declining then returning to normal values 3) Absence of ova (parasitologic cure) in repeated stool examinations in chronic cases 4) Decreasing antigenaemia / antibody levels 5) Disappearance or improvement of imaging findings
  • 32. Treatment efficacy • The detection of circulating Fasciola antigen & coproantigen is an efficient immuno-diagnostic tool to assess the effect of therapy in fascioliasis, as antigenaemia in the host reflects an active infection • Role of antibody detection to assess treatment efficacy is controversial.
  • 33. • Individuals who do not respond to oral drug therapy can be treated successfully by biliary drainage & the take out of worms or by flushing of the biliary system with povidone iodide
  • 34. The epidemiological picture of the disease has changed in recent years.
  • 35. There is a significant positive association between human fascioliasis & schistosomiasis mansoni
  • 38. 1. Periodic examination / treatment of livestock 2. Control of the snail vectors 3. Health education. 4. People must be aware of how infection might occur.