Diagnosis and treatment of Viral Peritonitis

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Diagnosis and treatment of Viral Peritonitis

• Bill Salzer
• University of Missouri
• 2/20/07
• salzerw_at_health.missouri.edu

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Culture Negative PD Peritonitis

• About 20 of cases are culture negative
• Causes
• Current or recent antimicrobials
• Fastidious organisms
• Chemical/inflammatory
• ?Viral

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Viral Peritonitis in PD Patients

• Not much out there
• Extensive literature search
• Consulted with the experts
• Found 3 reported cases

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Case1Striijk DG.Nephron 198644384

• 42 yo F, diabetes, failed transplant 1 year prior
• One week prior- son had a febrile, viral-like
  illness
• Presents with abdominal pain, cloudy fluid
• Peritoneal WBC 100-400, atypical inclusions
• Routine cultures and gram stain negative
• Dialysate grew virus on days 3-23, stool as
  well
• Echovirus 11- enterovirus group
• Clinically resolved by day 9

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Case 2Lewis SL. AmJKidneyDis 199117343-5

• 45 yo F, GI bleeds, interstitial pneumonitis,
  prednisone
• Multiple PRBC transfusions (3/87)
• 2-3 weeks- leukocytosis, LFT abnormalities
• Then 6 episodes of culture- peritonitis in 5
  months
• Cloudy fluid, WBCs- lymphocytes with atypicals
• Dialysate grew CMV in 9/87
• Serum CMV IgG was in 3/87, in 9/87
• 10/87, catheter changed, subsequently CMV -

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Case 3Yakulis R. ClinInfectDis1999281212-5

• 60yo F, DM, TAH for uterine mesodermal tumor-6mo
• Presents with abdominal pain, cloudy fluid
• Fluid- 100 wbc, PMN-2, lymph-64, mono-32
• Became febrile, severe abd pain, SBO, Cdiff
• Ex-lap d16- friable, necrotic omentum
• HSV on histology, no viral cultures done
• Acyclovir on d26, afebrile
• Died d 30

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Viral peritonitis- Cases in review

• Case 1 Echovirus 11
• Mild peritonitis
• Incidental infection?
• Case 2 CMV
• Patient on prednisone
• Primary infection from transfusion
• Persisted 5-6 months
• Case 3 HSV- fatal
• Severe disease
• Recent malignancy- ? Chemo or rads

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What is a virus?

• A bag of DNA or RNA looking for a cell to infect
• Obligate intracellular parasites
• Require a cells machinery to replicate
• Most are species specific, receptors, cells
• Immune response/immunity
• Viral antigens expressed on surface of infected
  cells
• CMI- CD4s, CD8s, CTLs, NK cells

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Pathogenesis of Viral Peritonitis

• Infection route- nose, mouth, skin, percutaneous
• Must encounter and bind to cellular receptors
• Peritoneum- mesothelial cells, macs, WBC
• Enter via the catheter?
• Viremia with many
• Cytolytic or not
• Inflammatory response- cytokines, wbc, etc,

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Viral peritonitis- the Unknown

• Absence or proof is not proof of absence?
• Does it occur and how often?
• Culture negative, lymphocyte predominance
• Viral cultures of dialysate
• ? PCR, which ones
• We need more data!

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Varicella-Zoster Virus

• Respiratory spread (varicella)
• Incubation 10-21 days, most 14 d
• Infectivity, infectiousness
• Chicken pox
• More severe in adults, immunocompromised
• Latency in dorsal ganglion
• Reactivation- zoster (shingles)

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Herpes Zoster- Shingles

• Latent in Satellite cells,neurons of dorsal
  ganglion
• Reactivation- age, CMI, trauma
• Prodromal sensory symptoms
• Unilateral dermatomal vesicles
• Thoracicgt lumbargt cervical
• Trigeminal, V1- keratitis
• Complications
• Post-herpetic neuralgia
• Disseminated in compromised host

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Acute Zoster R T-7 NEJM 347341
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Varicella- Prevention

• Vaccination- childhood, susceptible adults and
  teens
• Schools, health care facilities
• Live, attenuated Oka strain- approved in US 1995
• Kids 1 dose, gt 12yo 2 doses 4-8 weeks apart
• 85 effective, milder disease in vaccinees
• Rash 5-15, fever
• Immunocompromised- rash 40-50
• Pre-transplant
• Pediatric dialysis patients

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Zoster Vaccine

• Live attenuated Oka strain
• Much higher titer (15X) than varicella vaccine
• Oxman NEJM 20053522271
• Adults gt 60 YO, excluded immunocompromised
• Enrolled 38,500 pts, followed 3 years
• Overall reduced zoster 51, gt70yo-38, lt70-64
• Problems
• Costly, ?third party payers
• Duration of protection?
• Response in ESRD patients

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Kaplan-Meier Estimates of the Effect of Zoster
Vaccine on the Cumulative Incidence of
Postherpetic Neuralgia (Panel A) and Herpes
Zoster (Panel B) in the Modified
Intention-to-Treat Population
Oxman M et al. N Engl J Med 20053522271-2284
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Influenza virus

• Orthomyxovirus, enveloped, 80-120nm
• Ss RNA, linear but in 8 pieces
• Types A and B, C
• Yearly epidemics in winter
• Type As- hemagglutinin (H) and neuraminidase (N)
• Recombination with animal strains in Asia?
• Antigenic Drift- minor changes in H or N year to
  year
• Antigenic Shift- New H or N- pandemic
• World-wide, wide spread, severe disease

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Transmission andNatural History

• Spread by virus-laden respiratory secretions from
  an infected to a susceptible person
• Community spread of influenza typically produces
  a bell-shaped curve of reported cases and usually
  lasts 6-8 weeks
• Affects 15 of the US population annually
• Illness attack rate is highest in children,
  ranging from 14-40 yearly
• The elderly are also highly susceptible nursing
  home attack rates can approach 60

Zimmerman RK. J Fam Pract 199745107-24.
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Influenza Clinical

• Incubation 1-2 days, abrupt onset of symptoms
• Fever, malaise, myalgia, headache, eye ache
• Dry cough, rhinitis, sore throat
• Pneumonia- primary viral, secondary bacterial
• COPD, Asthma, CHF exacerbation
• Myositis/rhabdo, TSS, Reyes (ASA)
• DX- clinical, antigens (respiratory), cultures

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Influenza in ESRD

• Increased risk of severe disease, complications
• Vaccinate each fall
• Response to vaccine is decreased in ESRD
• Vaccinate all staff, dialysis units etc
• ? Vaccinate all close household contacts
• ? Flu mist- live virus vaccine, intranasal

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Influenza Vaccination

• Trivalent - 2 type A and 1 type B
• Effectiveness of influenza vaccination depends
  upon
• degree of similarity between the virus strains in
  the vaccine and circulating virus
• age and immune status of the vaccine recipient
• 60-80 in healthy young adults
• 20-30 in the elderly
• 50-60 in preventing hospitalization and
  pneumonia
• Protection
• only when good match and circulating viruses
• annual re-vaccination required

MMWR 200049(RR-3)1-38.
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Amantadine, Rimantadine

• PO, active on influenza A only
• Blocks M2 protein-ion channel, viral uncoating
• Resistance- 1AA change in M2 transmembrane
• 2005-6 H3N2 strain- 92 resistant
• Amantadine- renal, rimantadine hepatic
• Amantadine dose must be reduced with low GFR
• Treatment and prophylaxis of influenza A
• Side effects
• CNS (AgtR)- dizzy, nervous, mental status changes
• gt in elderly, renal dysfunction- reduce dose
• Anorexia, nausea, vomiting

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Zanamivir, Oseltamivir

• Neuraminidase inhibitors- influenza A and B
• NA cleaves sialic acids- receptor for HA
• Resistance- mutation in NA or HA
• Zanamivir- inhaled powder- bronchospasm
• Oseltamivir- PO- nauseavomiting- food reduces
• No dose adjustment for patients on dialysis
• Treatment- begin ASAP- (lt36-48hours)
• Prophylaxis
• ? Bird flu- oseltamivir resistance reported

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Emergence of New Influenza A Virus Subtypes in
Humans
Gerberding, J. L. et. al. N Engl J Med
20043501236-1247
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The Two Mechanisms whereby Pandemic Influenza
Originates
Belshe, R. B. N Engl J Med 20053532209-2211
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Generation of New Influenza A Virus Subtypes with
Pandemic Potential
Gerberding, J. L. et. al. N Engl J Med
20043501236-1247
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Avian influenza

• Current human strains- H1, H2, H3
• 1997- Hong Kong- H5N1- 18 human cases, 6 deaths
• 1999- Hong Kong- H9N2- mild
• 2003- Hong Kong- H5N1- 2 CASES, 1 DEATH
• 2003- Dutch- H7N7 89 human cases, 1 death
• 03-04- Asia H5N1, high mortality (80 in Hanoi)
• 2006-At least 2 H5N1 clones circulating
• Poultry, ducks, chickens
• Affect healthy adults and children
• Possible human to human transmission-family

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Avian Influenza- 2/07

• Birds, wild and domestic- Asia, Europe, Africa
• Epidemic strain- vs others
• Human cases- Asia, Mideast, Africa
• As Of 2/07- about 250 human cases, 55mortality
• Humans- close contact with infected birds
• Healthy adults, kids- fulminant disease
• Maybe 1 documented human to human
• Vaccine development ongoing
• Drug therapy?