Infectious Disease Case Conference

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Infectious Disease Case Conference

• Pimpawan Boapimp, MD
• Infectious Diseases Fellow
• April 5, 2004

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• 24 y/o arabic female
• H/O gestational trophoblastic tumor completed a
  treatment with chemotherapy one year ago
• Was referred from OSH for further management of
  abnormal CT abdomen
• C/O intermittent but mild right-sided abdominal
  and flank pain for one month
• 3 days PTA, pain became significantly worse

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• Unable to eat secondary to anorexia and nausea
• Few episodes of emesis with gastric contents
• Pain had been constant for 2 days, 10/10 in
  severity, worsened by movng, partially relieved
  by morphine in ED before transfer
• Fever for the last one week for which she took
  Tylenol for pain and fever

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• SHX immigrated from Kuwait 5 years ago
• frequently exposed to livestock animals
  as well as dogs while she was in Kuwait
• lives in Lexington
• no h/o travel out of NC
• no tobacco, no ETOH, no drug
• All NKDA
• FHX mother- breast CA

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• ROS 4-5 lbs weight loss over several
  months
• generalized fatigue
• LMP was 3 weeks ago
• otherwise negative

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PE

• VS T 100.3 P 104 RR 18 BP 102/68 RA
• GA a thin but healthy-looking woman,
• A O x 3, NAD, febrile
• HEENT PERRLA, EOMI, anicteric sclera
• Chest CTA bilaterally
• Heart RSR, no murmur
• Abd BS , marked tenderness with
  voluntary guarding in RUQ and Rt CVA

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• Abd Liver span 7-8 cm by percussion
• NS no focal deficit
• Skin no rash

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Laboratory Data

• CBC wbc 5.5 Hb 8.4 Hct 25.1 Plt 321
• N 77 L 17 E 0
• BMP WNL
• LFT alb 3.1 AST 23 ALT 28 ALP 300
  TB 1.6

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• HBs Ag NEG
• Anti HBc IgG NEG
• Anti HCV IgG NEG
• Anti HAV IgG NEG
• Anti HIV Ab NEG
• Transferrin 240 212-360
  mg/dl
• Iron 12 L 40.0-160 mcg/dl
• Ferritin 95 20-200
  ng/dl
• TIBC 343 230-500
  mcg/dl
• Saturation 3

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CT ABDOMEN
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Differential Diagnosis
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• Echinococcus Ab POSITIVE

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• Pt was treated with albendazole 400 mg PO BID
• Surgery was consulted
• Pt was admitted again few days after D/Cd home
  before the next appointment with surgery because
  of worsening abd pain
• Underwent open drainage of multiple hydatid cysts
  of the liver without any complications
• D/Cd home 5 days after surgery

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Echinococcosis

• Epidemiology
• -Life cycle
• Treatment
• New trend of treatment

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Echinococcal disease

• Caused by infection with the metacestode stage of
  tapeworm Echinococcus
• Family Taeniidae
• Four species
• E. granulosus , E. multilocularis - most common
• E. vogeli , E. oligarthrus - polycystic
  echinococcosis - rarely been associated with
  human infection.

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E. granulosus
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E. multilocularis
foxes
rodents
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• Worldwide
• Prevalence of infection varies widely among
  different countries and in different areas,
  ranging between 1 and 220 per 100,000
• Age-specific prevalence of liver and pulmonary
  hydatid cysts increases with advancing age

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• sheep strain is the most common cause of human
  infections
• Areas in which sheep are raised tend to have a
  higher rate of endemic disease.
• Transmission frequently occurs when dogs are fed
  the viscera of home-slaughtered animals. The dogs
  then excrete infectious eggs in their feces
•     

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• Modes of transmission
• - Contamination of the environment, including
  fields, water and cultivated vegetables  -
  Direct contact with infected pet dogs through
  fecal-oral contact mainly occurs in children
• - Transmission via arthropod intermediaries
• Prolonged survival of the eggs in the environment
  for many months

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• Slow-growing cyst is surrounded by the
  periparasitic host tissue (pericyst)
• Acellular outer wall (multilaminated membrane or
  chitinous layer)
• - Effective barrier to inflammatory host cells
  and microorganisms
• - Inhibit penetration of parasitocidal agents

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• The inner germinative layer covers the inside
• Consists of viable pluripotent cells
  proliferate, and form large numbers of brood
  capsules containing protoscolices

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IMAGING

• Plain film
• may reveal calcification within a cyst
• But cannot detect uncalcified cysts
• is not the imaging technique of choice

• CT, MRI, and ultrasound are used to detect
  hydatid
• cysts and to evaluate their characteristics

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Computed tomography

• The best mode for determining the number, size
  and anatomic location of the cysts
• use to monitor lesions during therapy and to
  detect recurrences
• Many reports suggest that CT has a higher overall
  sensitivity than ultrasound 95 to 100
• Better than ultrasound in detecting extrahepatic
  cysts.
• It may be superior to ultrasound in determining
  complications such as infection and intrabiliary
  rupture

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Magnetic resonance imaging

• has no major advantage over CT for abdominal or
  pulmonary hydatid cysts, except in defining
  changes in the intra- and extrahepatic venous
  system
• is usually not required and not cost effective
• it may delineate the cyst capsule better than CT
  and may be better at diagnosing complications
• - cysts with infection
• - biliary communication

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• Both MRI and CT are useful in diagnosing
  echinococcal infection in other sites, i.e. brain
  

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ULTRASOUND

• Portable ultrasound are frequently used for
• screening patients in endemic area of
• E. granulosus infection, sometimes with
  confirmatory serologic testing to maximize the
  diagnostic yield

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ULTRASOUND

• International classification of ultrasound images
  in cystic echinococcosis for application in
  clinical and field epidemiological settings.Acta
  Trop. 2003 Feb85(2)253-61.
• WHO Informal Working Group.
• Record as cystic lesions (CL)
• Type CE 1-5

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• Carlo Filice (Pavia, Italy) emphasized that only
  active, and sometimes transitional cysts need to
  be treated

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E. multilocularis

• Immunodiagnostic tests are more reliable than for
  E. granulosus infections with sensitivity and
  specificity rates of 95 to 100
• Serology usually remains positive indefinitely in
  patients receiving chemotherapy
• May become negative within a few years following
  complete surgical resection
• Clinical recurrence is often associated with
  rising serologic titers. IgG1 and IgG4 antibodies
  are the most sensitive isotypes for monitoring
  the success of therapy.

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TREATMENT

• E. granulosus
• Surgery
• - Conservative
• - Radical
• PAIR (Percutaneous Aspiration-Injection-Reaspirati
  on Drainage)
• Chemotherapy
• - albendazole (better than mebendazole)

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Evolving Treatment of Cystic Echinococcosis
Surgery no longer Universally indicated

• The 51th ASTMH annual meeting in Denver
• Menezes, the President of International Society
  of Hydatidology stated that
• No widely agreed-upon criteria and methods of
  surgery
• Depends on characteristics of the pt and the cyst
  (number, size, location, stage) as well as the
  therapeutic resources available and the
  physicians experience
• Greatest effectiveness, least morbidity,
  mortality, and recurrence

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SURGERY

• Benefit of successful Sx
• - Immediate and total cure- with radical Sx
• - Entails greater perioperative risks (Sx,
  anaphylaxis shock, 2 spread of infection and
  recurrence)
• Two types of surgery
• Conservative Sx
• - Sterilization and evacuation of cyst contents,
  membranes (hydatidectomy)

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SURGERY

• Radical Sx
• - Complete removal of cyst including host
  capsule
• - Or hepatic resection (segmentectomy or
  lobectomy)

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SURGERY

• Contraindications
• - Patients whose general condition is very
  poor     - Patients at the extremes of age  
    - Pregnant women     - Patients with multiple
  cysts or cysts that are difficult to access  
    - Patients with dead or totally calcified
  cysts

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PAIR

• Percutaneous puncture of cysts is performed under
  ultrasound guidance
• aspiration of substantial amounts of cyst fluid
• injection of a protoscolicidal agent into the
  cyst cavity (usually hypertonic saline or
  ethanol)
• The cyst is then reaspirated after a period of at
  least 15 minutes

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PAIR

• For inoperable patients and for those who refuse
  surgery
• Can be used for relapses after surgery
• But should not be used in pts with inaccessible
  cysts or superficially located liver cysts ( risk
  of spillage into the abdominal cavity)
• Contraindicated for cysts with echogenic foci,
  inactive or calcified cysts, and cysts with
  biliary communication

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PAIR

• medical therapy should be initiated at least 4
  days prior to a PAIR procedure
• should be continued for at least one month
  (albendazole) or three months (mebendazole)
• It is also advisable to do an ERCP pre-PAIR and
  to perform post-aspiration imaging of the cyst
  using contrast to rule out possible communication
  with the biliary tree

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• Percutaneous aspiration-injection-respiration
  drainage plus albendazole or mebendazole for
  hepatic cystic echinococcosis a
  meta-analysis.Clin Infect Dis. 2003 Oct
  1537(8)1073-83. Epub 2003 Sep 23.
• Meta-analysis of literature published from
  1990-2001

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• 769 pts (663- albendazole-treated,
  106-mebendazole-treated)
• Dx based on clinical, radiographic, cytologic or
  parasitologic, and/or serologic grounds
• Pts who were pregnant or who had infected cysts
  were excluded
• All pts undergoing percutaneous drainage were
  treated with either albendazole or mebendazole
  before and after drainage

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• Criteria to define cure or success in PAIR Tx
• Clinical disappearance of symptoms
• plus gt 1 of the following
• -On real-time US-separation of endocyst from
  pericyst and rupture of 2 vesicles in
  multivesicular cysts, a gradual decrease in cyst
  size until disappearance
• -On CT, increase in density of cyst cavity
• -On serologic and parasitologic exam, neg titer
  lt1160 and absence of live protoscolices in fluid

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• Other forms of responses improvement
• Decrease in size lt 50 and/or successful Tx of gt
  1 cyst in pt who had gt 1 cyst
• Recurrence- volumetric increase of a cyst and/or
  appearance of a cyst in the same or other organ
  after successful Tx
• Pts were observed for 6 months, US and/or CT,
  titers

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• Era-matched (1990-2001) historical control
  subjects who had undergone Sx
• 952 subjects
• Both conservative and radical Sx

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RESULTS

• PAIR-treated subjects
• Received pre-drainage albendazole or mebendazole
  for a median of 7 days
• and postprocedure drug therapy for a median of 28
  days
• Median duration of F/U was 20.5 months
• Mean duration of hospital stay was 2.4 days
• Titers of IgM and/or IgG decreased or reverted to
  neg after successful drainage

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RESULTS

• From control subjects
• 419 pts received albendazole or mebendazole in
  addition to Sx
• 533 pts underwent Sx alone
• Mean duration of F/U was 32 months
• Mean duration of hospital stay was 15 days
• (p lt .001, compared with PAIR-treated subjects)

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RESULTS

• Major reactions (i.e., anaphylaxis, cyst
  infection, liver or intra-abd abscess, sepsis,
  and biliary fistula) occurred in 7.9 of
  PAIR-treated subjects and 25.1 in Sx control
  subjects (p lt .0001)
• Minor reactions occurred in 13.1 of
  PAIR-treated subjects and 33 in Sx control
  subjects (p lt .0001)

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RESULTS

• No instance of dissemination (peritoneal seeding)
  by PAIR
• Fever (5.5 and 2.5 p lt .002) and allergic
  reaction (4.8 and 0.1 p lt .0001) were found
  more frequently in PAIR-treated subjects
• Clinical and parasitologic cure occurred in 95.8
  in PAIR-treated subjects and in 89.8 in Sx group
  (p lt .0001)

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• 29 pts with 240 cysts
• US showed a significant effect of albendazole
  with a cure rate about 10
• Size reduction of the metacestode in 60
• Changes in morphological appearance indicating
  degeneration in 62
• Pts with larger cysts and those with pul
  involvement were better responders.

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• Age and gender had no effect on outcome.
• Conclusion
• Albendazole should be offered to pts before Sx

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• 15 years experience with PAIR at the University
  of Pavia (Italy)
• 93 PAIR procedures on 68 echinococcal cysts in 57
  pts had been performed as of July 2002
• No associated instance of anaphylactic shock or
  chemical cholangitis was reported.
• Minor complications
• 4 cases of 2 bacterial infection of the cyst
• 1 case of fistulization into GB

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• 3 cysts relapsed after 4,5 and 11 years of F/U.
• The most important limitation of percutaneous Tx
  has to be stage-specific
• Multi-vesiculated cysts are associated with high
  risk of recurrence.

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• The choice of radical or conservative Tx depends
  on the experience of physicians
• Schantz observed that the introduction and
  widespread use in most echinococcus-endemic areas
  of imaging technology capable of diagnosing
  echinococcal cysts before they become symptomatic
  and complicated has greatly changed the spectrum
  of morbidity

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• Serology titers usually fall 1-2 years after
  successful surgery and will rise again if
  recurrence or secondary lesions develop

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RESULTS

• Disease recurrence occurred in 1.6 and 6.35,
  respectively (p lt .0001)
• 1 procedure-related death due to anaphylaxis
  (0.1) in PAIR group and 7 deaths (0.7) in Sx
  group (p lt .0827)
• Compared with Sx, PAIR plus chemotherapy is
  associated with greater clinical and
  parasitologic efficacy lower rates of morbidity,
  mortality, and disease recurrence and shorter
  hospital stays.

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• Limitations or biases include a shorter F/U
  period in PAIR group than in Sx group
• Only 3 of 21 PAIR studies had appropriate Sx
  control subjects

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