Investigation of Severe, Acute Hematochezia in Chimpanzees (Pan troglodytes)

1
Investigation of Severe, Acute Hematochezia in
Chimpanzees (Pan troglodytes)

• North America

2
Summer 1996
The method of entering the animals gender into
computer programs is MALE . FEMALE. UNKNOWN So,
a male is denoted as 1.0.0 Female 0.1.0 Unknown
0.0.1 Multiple animals can be entered in this way
as well. 1.1.0 would denote 1 male, 1 female, 2
animals total. This entire troop could be
denoted as 1.3.1

• A 1.0 Adult (35yr)
• B 0.1 Adult (45yr)
• C 0.1 Adult (32yr)
• D 0.1 Adult (17yr)
• E 0.0.1 Juvenile (3yr)

3
Environment

• Flooring Concrete
• Enclosure Metal bar surrounding structure
• Substrate NO natural substrate
• Atmosphere Open to outside, sealed from public
  areas

4
Diet

• Complete commercial biscuit
• Fed to age/weight
• Produce (varied)
• Leafy greens
• Vegetables
• Produce
• Free choice water
• Daily multivitamin
• Once monthly pyrantel pamoate by weight of animal
  for Enterobius control

5
Index Case-Summer 1996

• Day 1
• Early morning
• Quiet, not interested in food
• Mid-morning
• Diarrhea
• Liquid, but solid debris of apparently undigested
  food items
• Frequent bowel movements throughout day
• Sticky, sweet, pervasive odor

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Index Case-Day 1

• Treatment
• Oral electrolyte replacement
• Well-accepted
• Pepto-bismol
• Not accepted

• Fecal submitted
• O P
• Direct smear
• Stained smear

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Fecal results

• 2 cysts Balantidium coli
• Heavy epithelial cell population
• Some RBCs
• Moderate WBCs

Phagocytized bacteria in WBC
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Index Case-Day 1

• Late Afternoon
• Progressive lethargy, inappetance
• Plan for further diagnostics in morning if
  progression
• Early Evening
• Prostration
• Copious diarrhea, hematachezia
• Tacky, hyperemic gingiva

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Index Case-Day 1 Evening

• Treatment
• Sedated with Telazol
• IV catheter
• 0.9 saline
• LRS
• Cefazolin
• Banamine IM

• Diagnostics
• Blood Draw
• CBC, Biochemistry
• Temp 101.0 F
• Rectal culture

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Diagnostic tests for Great Ape Hematochezia

• Fecal culture
• Gold standard
• Fecal smear/Direct stain
• Within outbreak
• Fecal OP
• Parasite loads

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Bacterial Causes of Hematochezia in Great Apes

• Shigella
• Salmonella
• Campylobacter
• Yersinia
• Acha, P.N., and B. Szyfres. Year. Shigellosis.
  In Zoonoses and communicable diseases common to
  man and animals, 3rd ed., vol. 1. Pan American
  Health Organization, Washington, D.C. 247-251.
• Paul-Murphy, J. 1999. Bacterial enterocolititis
  in nonhuman primates. In Fowler, M.E., and R.E.
  Miller (eds.) Zoo and Wild Animal Medicine, 4th
  ed. Pp 344-351.

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CBC, Biochemistry Results

• Left shift
• Azotemia
• Hypokalemia
• Acidotic

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Questions

• What is your case definition?
• Is this a potential outbreak?

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Case Definition

• Lethargy
• Hematochezic diarrhea with undigested food
  apparent
• Stained smear of feces with WBCs, RBCs, and
  epithelial cells

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Potential Outbreak?

• Have great apes ever produced hematochezia at any
  zoo?
• YES
• Have great apes ever produced hematochezia at
  this zoo?
• YES
• How many great apes would you expect with
  hematochezia at this time?
• Expected nlt1 as occasional great ape may have
  hematochezia at this zoo for other reasons
• NO, not an outbreak

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INDEX CASE
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Day 2 Subsequent Cases

• (E) presented weak and clingy to dam C who
  appeared normal
• Diarrhea not present initially but fecal
  collected
• Diarrhea began midday in both E and C
• Both sedated with Telazol for diagnostics,
  fluids, antibiotics presumptively

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Day 2 of Index Case (A)

• Remained weak
• Diarrhea continued
• Treatment continued
• Balanced electrolytes by mouth
• No food
• IM antibiotics and anti-inflammatories

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Questions

• Do these new animals meet the case definition
  from yesterday?
• What is your revised case definition from
  clinical diagnostics?
• Is this a potential outbreak?

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Do these new animals meet the case definition
from yesterday?

• Partially
• Lethargy and diarrhea present
• Hematachezia NOT present
• Fecal smear RBCs, WBCs NOT present

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What is your revised case definition from
clinical diagnostics?

• Diarrhea of any sort within this given time frame
• Stained smear of feces with WBCs, RBCs, and
  epithelial cells

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Is this a potential outbreak

• Have great apes ever produced hematochezia at any
  zoo?
• YES
• Have great apes ever produced hematochezia at
  this zoo?
• YES
• How many great apes would you expect with
  hematochezia at this time?

23
How many great apes would you expect with
hematochezia at this time?

• All of troop, with 3 animals similarly affected,
  expected n?1 is exceeded

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Hematochezia diagnosis

• Fecal smear/direct stain--within outbreak
• WBCs (neutrophils)
• Sloughed intestinal mucosa
• RBCs
• Twice yearly fecal OP for parasite loads,
  treatments
• Appearance grossly
• Watery, mucoid, undigested material
• Odor is nearly pathognomonic
• CBC
• Left shift with neutrophilia, leukocytosis
• Biochemistry--consistent with dehydration
• Azotemia, hyperkalemia

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Day 3

• (A) Shigella sonnei cultured
• A,C,E continued on treatment

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Shigella sp.

• 4 serovars S. dysenteria, S. sonnei, S.
  flexneri, S. boydii
• S. dysenteriae and S.sonnei are nearly
  exclusively human source although they can infect
  NHPs
• S. flexneri is nearly exclusive NHP source, but
  can infect humans
• Gram--, non-motile bacilli bacteria that
  penetrates the colonic mucosa
• Can identify specific isolates by DNA
• Feco-oral transmission
• Short incubation period, 1-few days, contagious
• Sensitive to disinfectants

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Day 4

• C, E Shigella sonnei cultured
• Diarrhea abated over the following 24 hours, odor
  abated as well

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Day 5

• B,D Remained sub-clinical with only softened
  feces of normal appearance otherwise
• BUT, due to potential outbreaks feces were
  cultured and stained smear examined
• 3 days later S. sonnei cultured

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Questions

• Do these new animals meet the case definition
  from yesterday?
• What is your revised case definition from
  clinical diagnostics?
• Is this a potential outbreak?

30
Do these new animals meet the case definition
from yesterday?

• Partially
• Softened feces
• Culture for S. sonnei

31
What is your revised case definition from
clinical diagnostics?

• Diarrhea of any sort within this given time frame
• Stained smear of feces with WBCs, RBCs, and
  epithelial cells
• Culture of Shigella sonnei

32
Is this a potential outbreak?

• Have great apes ever produced hematochezia at any
  zoo?
• YES
• Have great apes ever produced hematochezia at
  this zoo?
• YES
• How many great apes would you expect with
  hematochezia at this time?

33
How many great apes would you expect with
hematochezia at this time?

• With 3 animals confirmed and 5 animals affected,
  expected n?1, as occasional great ape may have
  confirmed hematochezia at this zoo for other DDX
  but none for Shigella at the zoo, outbreak
  confirmed

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Details of outbreak

• ALL chimpanzees cultured S. sonnei
• ALL chimpanzees sedated, placed in squeezes for
  14 day treatment of IM cefuroxime based on
  sensitivity to 3rd generation cephalosporins
• 100 attack rate
• Curve shape suggests a point source
• Curve shape suggests resolution as all animals
  affected, no new cases, and responding to
  treatment
• Notice that treatment begins BEFORE outbreak
  concluded

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Antibiotic treatment and choices

• Important to complete culture/sensitivity
• Sensitivity is still routine to 3rd generation
  cephalosporins, quinolones
• Antibiotic resistance is easily developed
• Rehydration is important
• Anti-endotoxic regimens (Banamine)/anti-inflammato
  ries/analgesics can be used
• NO anti-diarrheals (traps toxins and bacteria)
• Administration options are challenging
• If parenteral, dart vs. squeeze
• If oral, unreliable consumption
• Shedding may be reduced by treatment in epizootic

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Resolution of signs

• Clinical signs resolved completely within the 1st
  seven days of treatment
• Following treatment, chimp troop was reunited
  without incident or recrudescence of disease

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End of Scenario?

• In the clinical sense, the scenario is done.
• The problem was diagnosed and resolved
• The epidemiology was strictly CONTROL

38
Looking Beyond

• Where did this outbreak originate?
• What permitted all 5 animals to become infected?
• Could it happen again?
• The epidemiology now becomes PREVENTION
• Stopping the investigation with here and now,
  will leave you vulnerable to WHY and HOW!

39
Long term effects of Shigella in NHPs

• Carrier status
• Reactive arthritis
• Gingivitis (macaques)
• Other NHPs infected, including humans

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Carrier Status

• Can be induced by inappropriate antibiotic choice
  or duration
• Minimal clinical signs support not treating to
  minimize development of a carrier state
• Potential environmental contamination with
  keepers/staff becoming fomites to other NHPs
• Natural exhibits are virtually impossible to
  disinfect
• Stress can induce recrudescence of infected
  carriers

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Food sources/Reservoirs

• Anthropormorphic view of how humans consume
  bananas
• Peeled, chimps consumed unpeeled
• Other unpeeled produce was cut and animals rarely
  consumed peels entirely
• Produce source Mexico
• HACCP
• Hazardous Analysis of Critical Control Points
• Food safety monitoring that will be critical to
  zoo food supplies and will minimize/prevent
  source issues like these
• Documentation that simply washing water is
  good/better than disinfectants for this organism

42
Environmental Investigation

• People, Source, Equipment
• Remember, feco-orally transmitted
• Rectal culture of commissary workers --gt neg
• Rectal culture of chimpanzee caretakers --gt neg
• Review of commissary procedure
• Unpeeled bananas were NOT being washed

43
Zoonoses and Control

• Concern for NHP caretakers
• Appropriate personal hygiene and protection is
  key
• COMMUNICATION will prevent transmission to other
  NHPs and humans
• Risks
• Protection

44
Quarantine MeasuresWithin Outbreak

• Review of personal hygiene
• NO eating/drinking in area
• Washing hands
• PPE
• Masks, gloves, dedicated coveralls, dedicated
  boots, dedicated daily caretakers
• Daily disinfection with phenol based products
• Tools, holding areas
• Foot baths with phenol based products
• Pest control measures stepped up in area
• Minimize mechanical carriers

45
Onset-Presentation

• Age stratum
• Smaller body weight and younger animals seemed
  most susceptible rather than aged animals
• Troop Status
• Male received most of the bananas
• Infant would have dose issues as well as favored
  status
• Clinical signs
• Lethargy, febrile, diarrhea, abdominal pain, and
  reduced appetite
• Can be fatal epizootics
• IMPORTANT to prevent
• through food hygiene

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Setting the Stage for Future Outbreaks

• Summer 1997
• A 1.0 Adult (35yr)
• B 0.1 Adult (45yr)
• C 0.1 Adult (32yr)
• D 0.1 Adult (17yr)
• E Juvenile (3yr)
• F Juvenile (8 yr)
• G Juvenile (7yr)

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History

• 1.1 Chimpanzee (hand-reared)
• Considered for integration into this troop
• History of Shigella sonnei cultured
  intermittently throughout their first years of
  life with minor clinical signs and response to
  antibiotics (p.o., multiple
• courses)

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Prevention Considerations

• Pre-shipment examination
• CBC, chemistry panel (Within normal limits)
• Rectal cultures (negative for Shigella)
• Quarantine examination included
• CBC, chemistry panel (WNL)
• Rectal culture (negative for Shigella).
• Approach for original troop
• Remains similar to post-outbreak

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Quarantine MeasuresLong Term

• Review of personal hygiene (NO eating/drinking in
  area, washing hands)
• PPE (masks when feces aerosolized, gloves w/
  contact with feces, dedicated coveralls,
  dedicated boots, dedicated daily caretakers)
• Routine disinfection of tools, holdings with
  phenolic based products
• Dedicated tools to affected area
• Foot baths with phenolic based products
• RE-washing all produce daily (zoo wide)

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Break-Out Disease and Response

• Improved due notes and reports of the complete
  prior investigation confirming that carriers
  occurred in one or both troops!
• After 45 days, G was introduced to C and E
• Diarrhea within 72 hours from G culture
  positive for Shigella sonnei.
• ALL chimpanzees placed on p.o. cefapirin for 10
  days before introduction proceeded.

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Break-Out Disease and Response

• NO additional episodes of diarrhea during
  introduction and no additional Shigella cultures
  for the following three years. Infant born 18
  month after introduction completed (C and F) and
  no clinical shigellosis occurred in dam or
  infant.
• Transfer at 24 months following introductions
• No clinical shigellosis occurred.
• However, troop and exhibit were maintained as
  carrier-status
• Justified by break out and zoonotic concern

52
References

• 1. Acha, P.N., and B. Szyfres. Year.
  Shigellosis. In Zoonoses and communicable
  diseases common to man and animals, 3rd ed., vol.
  1. Pan American Health Organization, Washington,
  D.C. 247-251.
• 2. Banish, L.D., R. Sims, D. Sack, R.J. Montali,
  L. Phillips, and M. Bush. 1993. Prevalence of
  shigellosis and other enteric pathogens in a
  zoologic collections of primates. J Am Vet Med
  Assoc 203(1) 126-132.
• 3. Banish, L.D., R. Sims, M. Bush, D. Sack, and
  R.J. Montali. 1993. Clearance of Shigella
  flexneri carriers in a zoologic collection of
  primates. J Am Vet Med Assoc 203(1) 133-136.
• 4. Gravani, R.B., and E.A. Bihn. 2001. Good
  agricultural practices program fruit and
  vegetable microbiological safety issues.
  http//www.gaps.cornell.edu.
• 5. Ketz-Riley, C.J. 2003. Salmonellosis and
  shigellosis. In Fowler, M.E., and R.E. Miller
  (eds.) Zoo and Wild Animal Medicine, 5th ed. Pp
  686-689.
• 6. Nizeyi, J.B., R.B. Innocent, J. Erume,
  G.R.N.N. Kalema, M.R. Cranfield, and T.K.
  Graczyk. 2001. Campylobacteriosis,
  salmonellosis, and shigellosis in free-ranging
  human-habituated mountain gorillas of Uganda. J
  Zoo Wildl Med 37(2) 239-244.
• 7. Paul-Murphy, J. 1999. Bacterial
  enterocolititis in nonhuman primates. In
  Fowler, M.E., and R.E. Miller (eds.) Zoo and Wild
  Animal Medicine, 4th ed. Pp 344-351.
• 8. Raiden, R.M., S.S. Sumner, J.D Eifert, and
  M.D. Pierson. 2003. Efficacy of detergents in
  removing Salmonella and Shigella spp. from the
  surface of fresh produce. J. Food Protection 66
  2210-2215.
• 9. Stetter, M.D., R.A. Cook, P.P. Calle,
  M..Shayegani, and B.L. Raphael. 1995.
  Shigellosis in captive western lowland gorillas
  (Gorilla gorilla gorilla). J Zoo Wildl Med
  26(1) 52-60.
• 10. Wolfensohn, S. 1998. Shigella infection in
  macaque colonies case report of an eradication
  and control program. Lab. Anim. Sci. 48
  330-333.