Importance of Vaccination Among Dialysis Patients: Vaccine Recommendations for Patients Receiving Di

1
Importance of Vaccination Among Dialysis
PatientsVaccine Recommendations for Patients
Receiving Dialysis

• Matthew J. Arduino, Dr.P.H.
• matthew.arduino_at_cdc.hhs.gov
• Division of Healthcare Quality Promotion
• National Center for Preparedness, Detection, and
  Control of Infectious Diseases
• Centers for Disease Control and Prevention

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Overview

• Vaccine Preventable Diseases
• Vaccine Preventable Disease in Dialysis Patients
• Hepatitis B Virus
• Pneumococcal Disease
• Influenza
• Vaccine Recommendations as Part of an Overall
  Infection Control Program
• Vaccination of Healthcare Personnel
• Healthy People 2010 Goals
• The Safe and Timely Vaccine Coalition

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Vaccine Preventable Diseases

• Anthrax
• Chickenpox
• Hepatitis B
• HPV
• Influenza
• Meningococcus
• Pertussis
• Polio
• Rubella
• Smallpox

• Diphtheria
• Hepatitis A
• HiB
• Measles
• Mumps
• Pneumococcus
• Rabies
• Shingles (Zoster)
• Tetanus
• Yellow Fever

4
Patients with CKD or ESRD

• Infections account for a large portion of
  hospitalizations among patients on dialysis
• Infection is the second leading cause of
  mortality among patients with ESRD
• Infections may contribute to cardiovascular
  disease and mortality

5
Immunity and Kidney Disease

• CKD and ESRD patients have decreased immune
  responses
• Uremia contributes to the impaired host response

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Host Defenses are Affected by the Uremic State

• Neutrophil function
• Neutrophils show decreased chemotaxis,
  phagocytosis, and intracellular killing.
  Ingestion and oxidative metabolism are decreased
  markedly and are not improved by hemodialysis
• Antigen processing
• Cell-mediated immune responses, T-cell, B-cell,
  and monocyte function are impaired, resulting in
  faulty presentation of antigens for immune
  recognition
• Antibody formation
• Alterations in the functional capacity of
  lymphocytes result in impaired antibody responses.

7
Disease Burden
8
Change in Hospital Admissions Since 1993
period prevalent dialysis patients rates
adjusted for age, gender, race, primary
diagnosis. ESRD patients, 2004, used as reference
cohort. Vascular access hospitalizations are
pure inpatient vascular access events, as
described in Appendix A.
USRDS 2006 ADR
9
Adjusted Admissions For Principal Diagnoses, By
Modality
period prevalent ESRD patients adjusted for age,
gender, race, primary diagnosis. ESRD patients,
2004, used as reference cohort.
USRDS 2006 ADR
10
Hepatitis B Virus
11
Risk Factors Associated with Reported Hepatitis
B, 1990-2000, United States
Other Surgery, dental surgery, acupuncture,
tattoo, other percutaneous injury
Source NNDSS/VHSP
12
Incidence and Prevalence of Hepatitis B in the
United States, 1976-2002
CDC Infection Control Recommendations (1977)
Vaccine (1982)
13
Sources for Bloodborne Virus infections in
Hemodialysis Patients

• External
• Transfusion from unscreened blood
• Non-dialysis related healthcare procedures
• Household/sex with infected contact
• Illegal injection drug use (more common in
  western countries)
• Internal
• Patient-equipment-patient (HBV HCV
  contamination on devices, tubing, supplies,
  surfaces)
• Patient-equipment-staff-patient (HBV HCV
  contaminated surfaces touched by staff transmit
  with contaminated gloves or hands)
• Patient-staff-patient ( direct contamination of
  staff members hands/gloves with blood)
• Contamination of multidose vials

14
Incidence and Prevalence of HBV Infection Among
US Dialysis Centers, 2002

• Incidence and prevalence has remained stable over
  the last decade
• 27.3 of centers reported gt 1 patients with
  chronic HBV infection
• 2.8 of US dialysis facilities reported gt 1
  patients with newly acquired HBV infection

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Resurgence of HBV Outbreaks in the mid 1990s
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Outbreaks of HBV in the Hemodialysis

• Simultaneous provision of care to both
  HBV-infected and susceptible patients by the same
  staff members
• Failure to identify and segregate infected
  patients from susceptible patients
• Failure to vaccinate susceptible patients
• Sharing of supplies and equipment
• Cross-contamination of environmental surfaces,
  supplies, or equipment
• Multiple dose medication vials

17
Preparation of Injectable Medications

• In 2002, 52.8 of centers reported that
  medications from multi-dose vials were prepared
  for patient administration in a dedicated
  medication room or an area separate from the
  treatment area
• 24.6 reported that medications were prepared on
  a medication cart or a medication area within the
  treatment area, 3.7 at the dialysis station, and
  18.9 in other areas
• the incidence of HBV infection was significantly
  higher among patients in centers where injectable
  medications were prepared on a medication cart or
  medication area located in the treatment area

18
Patterns Of Hepatitis B Prevalence And
Seroconversion In Hemodialysis Units From Three
Continents The DOPPS

• Protocol for HBV-infected patients was protective
• Hepatitis B virus vaccine not routinely
  administered at the unit (depending on the model
  2-11 fold higher risk)
• In 1977, the CDC in the United States issued a
  set of recommendations to control of HBV in
  hemodialysis units. The original recommendations
  were effective and most are still in place

Burdick RA, et al. Kidney Int 200363(6)2222-9.

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Streptococcus pneumoniae

• Major clinical syndromes
• Pneumonia
• Bacteremia
• Meningitis
• Asymptomatic human carriers (nasopharynx) act as
  a reservoir

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Pneumoccoal Pneumonia

• Pneumococcal infections kill more people in the
  United States each year than any other
  vaccine-preventable disease or the combined
  disease burden of other vaccine preventable
  diseases
• Community-acquired pneumonia is associated with
  significant morbidity and mortality and is the
  most common cause of death from infectious
  diseases in North America

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Pneumococcal Pneumonia

• 36 of adult community acquired cases of
  pneumonia
• 50 of hospital-acquired pneumonia
• Case fatality rate is 5-7 (higher in the
  elderly)
• Estimated 175,000 hospitalizations each year

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Burden of Disease

• Vascular access 20.8
• Infections below the knee 19.3
• Pneumonia 13
• Skin and soft tissue 9

Berman SJ. Johnson EW. Nakatsu C. Alkan M. Chen
R. LeDuc J. Burden of infection in patients with
end-stage renal disease requiring long-term
dialysis. Clin Infect Dis 2004 39174753
23
Bacterial Pneumonia and Dialysis Patients

• Dialysis Patients have 14-16 times higher
  pulmonary infectious (pneumonia) mortality rates
  compared with the general population.
• The relative risk for death at 6 months in
  first-year dialysis patients who experienced an
  episode of pneumonia was 5.1
• Relative risk for cardiovascular events in the
  first 6 months also was greater at 3.02

Sarnak MJ, Jaber BL. Pulmonary infectious
mortality among patients with end-stage renal
disease. Chest 2001120(6)1883-7. Dinits-Pensy
M, Forrest GN, Cross AS, Hise MK. The use of
vaccines in adult patients with renal disease.
Am J Kidney Dis 2005 46(6) 997-1011
24
Data from USRDS

• Hospitalization with pneumonia is common event
  (experienced by 33 of dialysis patients by 5
  years of follow-up).
• A microbiologic diagnosis was not specified in
  majority of cases
• Older age and comorbid diseases were associated
  with a gt risk of pneumonia
• Renal transplantation was associated with lower
  event rates.
• Hospitalization with pneumonia was associated
  with lower survival probabilities.

Slinin Y, Foley RN, Collins AJ. Kidney
International 2006 70 (6) 11351141.
25
KaplanMeier Estimates of Pneumonia-Free Survival
Probabilities In Non-Waitlisted and Waitlisted
ESRD Patients
Slinin Y, Foley RN, Collins AJ. Kidney
International 2006 70 (6) 11351141.
26
KaplanMeier Estimates of Survival Probabilities
After Pneumonia in Non-waitlisted and Waitlisted
ESRD Patients
Solid Line Non-waitlisted Dashed line Waitlisted
Slinin Y, Foley RN, Collins AJ. Kidney
International 2006 70 (6) 11351141.
27
Pneumococcal Vaccination Rates

• Relatively low vaccination rates
• Vaccination rate among dialysis patients 13.5

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Influenza

• TEM micrograph of the 1918 influenza virus

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Seasonal Influenza, United States

• Influenza epidemics have been responsible for an
  average of 36,000 deaths/year in the United
  States between 1990 and 1999
• gt 200,000 people are hospitalized with influenza
  complications
• Seasonal influenza rates vary from 5-20 a year
• Recent studies indicate Influenza epidemics are
  associated with a rise in autopsy-confirmed
  coronary deaths

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Influenza Vaccination

• Influenza vaccination rates in the general
  population have been increasing
• Vaccination rates in the ESRD population have
  remained well below the target of Healthy People
  2010

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Vaccination is an important tool for preventing
many infectious diseases
32
Available from http//www.cdc.gov/ncidod/dhqp/dp
ac_dialysis_pc.html
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Vaccination of Renal Dialysis Patients and
Patients with Chronic Renal Disease
34
Vaccine Preventable Diseases and Chronic Renal
Disease

• Patients with Renal failure have an increased
  risk of infection to a variety of pathogens
• Primary pathogens include Staphylococcus
  aureus, hepatitis B virus, Streptococcus
  pneumoniae

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The Use of Vaccines in Patients with Kidney
Disease

• Hepatitis B Virus
• Pneumococcal (Streptococcus pneumoniae)
• Influenza
• Tetanus Toxoid (either alone or in combination
  with Diphtheria)
• Varicella
• Hepatitis A Virus (In patients with existing
  liver disease)

Varicella vaccine is not recommended
post-transplant
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Routine Vaccinations in Children with Chronic
Renal Failure

• Children with CRF generally produce protective
  serum antibodies to primary vaccinations with
  killed or component vaccines and live virus
  vaccines
• Some children on dialysis and after transplant
  may not respond optimally, requiring repeated
  vaccination.
• Proof of vaccine efficacy is absence of disease,
  which can only be confirmed in large cohort
  studies.
• A few observational studies provide evidence that
  vaccination has contributed significantly, at
  least in the western hemisphere.

Neuhaus TJ. Immunization in children with
chronic renal failure a practical approach.
Pediatr Nephrol 200419(12)1334-9.
37
National Surveillance of Dialysis Associated
Diseases, 1995-2002
Despite the high mortality and increased
cardiovascular event rates associated with
pneumonia, immunization rates with pneumococcal
vaccine remain low
38
Hepatitis B Vaccine

• Hepatitis B vaccination is recommended for all
  susceptible chronic hemodialysis patients
• Vaccination is recommended for pre-ESRD patients
  before they become dialysis dependent
• Higher seroconversion rates and antibody titers
  occur in uremic patients prior to becoming
  dialysis dependent

39
Hepatitis B Vaccine-General Population ( For
Staff members)

• Licensed in 1982 currently recombinant (in US)
• 3 dose series, typical schedule 0, 1-2, 4-6
  months - no maximum time between doses (no need
  to repeat missed doses or restart)
• 2 dose series (adult dose) licensed by FDA for
  11-15 year olds (Merck)
• Protection 30-50 dose 1 75 - 2 96 - 3
  lower in older, immunosuppressive illnesses
  (e.g., HIV, chronic liver diseases, diabetes),
  obese, smokers

40
Immunogenicity HBV Vaccine

• Primary series produces a protective anti-HBs
  response in 90-95 of adults with normal immune
  status
• Proportion of patients with ESRD who develop a
  protective antibody response is lower
• For those receiving a 3-dose schedule the median
  is 64 (range 34-88)
• For those receiving a 4-dose schedule the median
  is 86 (range from 48-98)

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Immunogenicity and CKD/ESRD

• Studies indicate that it is better to begin
  vaccinating patients before they become dialysis
  dependent
• Adults with serum creatinine levels lt 4 mg/dl
  (mean 2 mg/dl) responded significantly (86)
  better than patients with serum creatinine levels
  gt 4 mg/dl (mean 9.5 mg/dl) (37).

Fraser GM, Ochana N, Fenyves D, et al.
Increasing serum creatinine and age reduce the
response to hepatitis B vaccine in renal failure
patients. J Hepatol 1994214504. Seaworth B,
Drucker J, Starling J, Drucker R, Stevens C,
Hamilton J. Hepatitis B vaccine in patients with
chronic renal failure before dialysis. J Infect
Dis 19881573327. Dukes CS, Street AC,
Starling JF, Hamilton JD. Hepatitis B vaccination
and booster in pre-dialysis patients a 4-year
analysis. Vaccine 199311122932.
42
HBV Vaccine Effectiveness

• Limited data are available on the duration of
  immune memory after hepatitis B vaccination in
  dialysis patients
• No clinically important HBV infections have been
  documented among immunocompromised persons who
  maintain protective levels of anti-HBs (gt10
  mIU/mL).
• Infections have occurred in individuals who have
  not maintained their anti-HBs (gt10 mIU/mL)

43
Doses and Schedules of Licensed HBV Vaccines for
Hemodialysis Patients
Dose recommended by FDA higher doses maybe more
immunogenic for hemodialysis patients
44
New Immunogenic Vaccine?

• Single doses of HB-AS04 (Fendrix, GlaxoSmithKline
  Biologicals)
• Engerix administered at 0, 1, 2, and 6 months,
  and followed-up for 36 months
• Patients with creatinine clearance lt30 mL/min
• HB-AS04 vaccine elicited a more rapid onset of
  protection than the currently licensed vaccine
  for this particular population, with 74 versus
  52 of subjects seroprotected at 3rd month
• After the vaccination course, seroprotection
  rates increased to 91 versus 84 in the HB-AS04

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Fendrix References

• Tong NK, et al. Immunogenicity and safety of an
  adjuvanted hepatitis B vaccine in
  pre-hemodialysis and hemodialysis patients.
  Kidney Int 2005 68(5)2298-2303.
• Nevens F, et al. Immunogenicity and safety of an
  experimental adjuvanted hepatitis B candidate
  vaccine in liver transplant patients. Liver
  Transpl 200612(10)1489-95.
• Boland G, e al. Safety and immunogenicity
  profile of an experimental hepatitis B vaccine
  adjuvanted with AS04. Vaccine 200423(3)316-20.
  

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Pneumococcal Vaccine

• Two Vaccines are available
• PPV23 (polyvalent containing 23 capsule
  serotypes)
• PPV7 (polyvalent, containing the 7 serotypes
  responsible for pneumococcal disease in children)

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Children and PCV7

• All children 6 months through 23 months of age
  should get PCV7 regardless of their health status
  as part of the routine childhood immunization
  schedule
• For children aged 24-59 months with underlying
  medical conditions ACIP recommends two doses of
  PCV7, administered 2 months apart, followed by
  one dose of PPV23 administered gt2 months after
  the second dose of PCV7.

48
PPV23 Use

• Persons with underlying medical conditions that
  place them at risk (includes CKD and ESRD
  patients)
• for persons aged gt2 years who are at highest risk
• for those at risk for serious pneumococcal
  infection and those who are likely to have a
  rapid decline in pneumocococcal antibody levels,
  a second dose of vaccine should be given at least
  5 years after the initial dose.
• Revaccination 3 years after the previous dose may
  be considered for children at highest risk for
  severe pneumococcal infection who would be aged
  lt10 years at the time of revaccination.

49
Pneumococcal Vaccine and CKD/ESRD

• Review of 26 published studies in this
  population, all studies demonstrated a serologic
  response by the majority of patients to at least
  some pneumococcal serotypes.
• Use of steroids did not alter this response.
• In the studies with a gt 6 month follow-up,
  declining antibody titers were consistently
  reported, and this decline was usually more rapid
  than in healthy controls.
• Incidence of serious adverse reactions to vaccine
  is very low.

Robinson J. Efficacy of pneumococcal
immunization in patients with renal disease--what
is the data? Am J Nephrol 200424(4)402-9.
50
Pneumococcal Vaccine Studies in Chronic Renal
Failure Patients

• Fuchshuber A, Kuhnemund O, Keuth B, Lutticken R,
  Michalk D, Querfeld U. Pneumococcal vaccine in
  children and young adults with chronic renal
  disease. Nephrol Dial Transplant
  199611(3)468-73.
• Furth SL, Neu AM, Case B, Lederman HM, Steinhoff
  M, Fivush B. Pneumococcal polysaccharide
  vaccine in children with chronic renal disease a
  prospective study of antibody response and
  duration. J Pediatr 1996 Jan128(1)99-101.
• Nikoskelainen J, Koskela M, Forsstrom J, Kasanen
  A, Leinonen M. Persistence of antibodies to
  pneumococcal vaccine in patients with chronic
  renal failure. Kidney Int 1985 Oct28(4)672-7.

51
Influenza Vaccine Response Among Dialysis Patients

• Efficacy of influenza vaccination in this
  population has been a point of debate
• Earlier studies showed an impaired response to
  influenza vaccination in patients with renal
  disease
• Recent literature shows that although the overall
  antibody response to influenza vaccination is
  diminished in dialysis patients, they can still
  mount a protective antibody response

52
Influenza Vaccine Delivery and Effectiveness in
ESRD, USRDS 1997-1999

• Influenza vaccination rates were lower in
  non-whites, women, younger patients, and
  peritoneal dialysis patients
• Influenza vaccination was associated with a lower
  risk for hospitalization and death

Gilbertson DT, Unruh M, McBean AM, Kausz AT,
Snyder JJ, Collins AJ. Influenza vaccine delivery
and effectiveness in end-stage renal disease.
Kidney Int 200363738743.
53
Influenza

• Patients with CKD or ESRD are a priority group
  for vaccination with inactivated influenza
  vaccine (TIV)
• Live, Attenuated Influenza Vaccine (LAIV) is
  contraindicated for these patients

54
Influenza and Healthcare Workers

• To reduce staff illnesses and absenteeism during
  the influenza season and to reduce the spread of
  influenza to and from workers and patients, the
  following HCWs should be vaccinated in the fall
  of each year
• Persons who attend patients at high risk for
  complications of influenza
• Persons aged 65 years
• Persons with certain chronic medical conditions
• Pregnant women who will be in the second or third
  trimester of pregnancy during influenza season.

CDC. Immunization of Health-Care Workers,
Recommendations of the Advisory Committee on
Immunization Practices (ACIP) and the Hospital
Infection Control Practices Advisory Committee
(HICPAC). MMWR 1997 46 (RR-18)1-42
55
Healthcare Workers

• Dialysis staff members (healthy persons) aged
  549 years in these groups who are not contacts
  of severely immunocompromised persons can use
  Live, Attenuated Influenza Vaccine (LAIV) (see
  Live, Attenuated Influenza Vaccine
  Recommendations) can receive either or
  inactivated influenza vaccine.
• All other persons in this group should receive
  inactivated influenza vaccine.

56
Live, attenuated influenza vaccine (LAIV)
compared with inactivated influenza vaccine
57
Hepatitis A Vaccine

• People with any type of chronic liver disease
  including patients with chronic HBV or HCV
• Injection and non-injection drug users
• Travelers to places with high rates of HAV
  infection (Africa, Central/South America, Asia,
  Middle East, Russia)
• Men who have sex with men
• People with clotting-factor disorders
  (hemophilia)
• People waiting for or who have had a liver
  transplant
• Children living in areas of U.S. with
  consistently increased rates of hepatitis A

58
2010 Healthy People Goals
http//www.healthypeople.gov/document/HTML/Volume1
/14Immunization.htm_Toc494510242
59
Safe and Timely Immunization Coalition (STIC)

• A national coalition of healthcare professionals
  and ESRD patients was formed in 2005
• Coalition includes representatives from dialysis
  providers, CDC, patient groups, network staff,
  QIOs, and others
• A special project funded by the CMS and CDC to
  increase the rate of Hepatitis B, influenza, and
  Pneumococcal immunizations in patients and staff
  in the dialysis setting
• Focused on immunization education, data
  collection, ESRD-specific guidelines, developing
  interventions to increase vaccination rates among
  dialysis patients.

60
STIC

• Facilities in ESRD Network 6, 11, and 15 are
  participating in the data collection phase of
  this project

http//www.esrdnetwork6.org/PatientResources/STICB
ook.pdf
61
STIC Goals

• Educate patients and staff about the importance
  of vaccine preventable diseases
• Improve vaccination rates among patients and
  staff
• Pneumococcal Vaccine- achieve the Healthy People
  2010 goals (90 of patients in high risk groups)
• Influenza (90 of patients in high risk groups)
• HBV (90 of patients in high risk groups)
• Vaccinate all susceptible patients
• Vaccinate all staff who have exposures to
  bloodborne pathogens

62
DHQP Web Resourceshttp//www.cdc.gov/ncidod/dhqp/
dsn.html
63
National Immunization Program Resourceshttp//www
.cdc.gov/nip/
64
Additional References

• CDC. Prevention and Control of Influenza,
  recommendations of the Advisory Committeee on
  Immunization Practices. MMWR 200655
  (RR-10)1-42.
• http//www.cdc.gov/mmwr/PDF/rr/rr5510.pdf
• ACIP Recommendations
• http//www.cdc.gov/nip/publications/acip-list.htm
  
• Safe and Timely Vaccine Coalition
• http//www.esrdnetwork6.org/PatientResources/STIC
  Book.pdf
•     

65
Protect patients,Protect healthcare
personnel,Protect quality healthcare
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