Vaccination in Immunosuppressed Adults
Transcript of Vaccination in Immunosuppressed Adults
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Vaccination in Immunosuppressed Adults
Clinical Vaccinology
Update
The Melbourne Vaccine Education Centre
14 Sep 2018
Professor Katie Flanagan
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Types of Immune Suppression to Consider
o Cancer and haematological malignancies
o Chronic diseases – diabetes, COPD,
autoimmune diseases
o Chronic infections – HIV
o Asplenia
o Physiological – pregnancy
o Stem Cell / Solid organ / bone marrow
transplant
o Drug induced
– Steroids
– Other immunosuppressive drugs –
methotrexate, azathioprine
– Cancer and haematological
malignancy treatments
o Immunotherapies
– Monoclonal antibodies
– Immune checkpoint inhibitors
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General Ruleso Immune compromised persons are at increased risk
of morbidity and mortality from many VPDs
o Degree of immune compromise should be assessed to determine vaccination strategy
o Inactivated vaccines are generally safe in the immunocompromised adult but not always as immunogenic / efficacious
o Live vaccines are contraindicated in many immunocompromising situations due to risk of disseminated infection, in particular: – BCG is always contraindicated– Other live vaccines should not be given to those
with severe immunocompromise
o Severe immunocompromise includes active leukaemia, lymphoma, generalised malignancy, recent chemo (last 3 months), aplastic anaemia, GVHD, BMT or solid organ transplant in last 2 years, transplant recipients still taking immunosuppressives, high-dose corticosteroids
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o Many vaccines can be given pre-emptively to people who anticipate immunocompromise in the future i.e. contemplating immunosuppressive therapy e.g. varicella zoster vaccine, pneumococcal vaccination
Influenza Vaccination
o Annual seasonal vaccination recommended for all immune compromised adults
o Should be given 2 doses at least 4 weeks apart the first time it is given
o In a pandemic situation 2 doses of vaccine may be given any season
General Rules
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Cancer / Haematology Patients
Live vaccines
o Contraindicated if on immunosuppressive therapy or have poorly controlled malignancy
o Avoid when neutropaenic (<0.5x109/L)
o Wait until 3 months after treatment and confirmed remission
Inactivated Vaccines
o Give annual influenza (2 doses 1st time)
o Give any required inactivated vaccines
o Haematological malignancy patients (lymphoma, leukaemia, myeloma) should be given pneumococcal vaccination – 1 dose of 13 valent PCV then 2 doses of 23 valent PPV 8 weeks after PCV
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Adult Cancer / Haematology Patients in Remission for >6 months
• Single dose dTpa
• Single dose MMR / IPV / HepB
(Check measles and rubella Abs 6-8 weeks after MMR and
revaccinate if non- seroconverter)
• Single dose 13vPCV then 2 doses 23vPPV
• Single dose Hib
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Solid Organ Transplant
o Live vaccines contraindicated
o Inactivated vaccines safe but often delayed until 6 months post-treatment to maximiseimmunogenicity
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Solid Organ Transplant
Vaccine Pre-Transplant Post-Transplant
(if not given before)
dTpa Yes Yes
IPV Yes Yes
HepA and HepB
Yes (depends on serostatus)
Yes (depends on serostatus)
13vPCV then 2 x 23vPPV
Yes Yes
MenACWY and MenB
Yes (if risk factors)
Yes (if risk factors)
Annual influenza
Yes Yes
MMR Yes No
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Haematopoietic Stem Cell
Transplant
Protective immunity to VPDs partially or fully lost post HSCT, particularly first 6 months
Autologous HSCT patients recover immunity more quickly & don’t get GVHD
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Haematopoietic Stem Cell Transplant
* Only if no ongoing GVHD and CMI has recovered
There is a role for donor immunisation with Hib, PCV, hepB and tetanus vaccines prior to harvest but rarely done
Vaccine Schedule
13vPCV 3 doses 6, 8, 12m post HSCT
23vPPV 1 dose 24m post HSCT
Hib / dTpa / IPV 3 doses 6, 8, 12m post HSCT
HepB 3 doses 6, 8, 12m post HSCTHigh dose formulation or dose in each arm each visit
4vMenCV and MenB 2 doses 6 and 8m
MMR * 24m - 1-2 doses (check Abs at 4wks)
Varicella * 24m - 2 doses 4wks apart if seronegative
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20mg prednisolone is equivalent to:
• 16 mg methylpred
• 16mg triamcinolone
• 3.2mg dexamethasone
• 80mg hydrocortisone
Prednisolone Equivalent Dose
Duration Timing of Vaccination
<20mg / day Any Give any time
≥20mg / day < 14 days 1 month before or any time
after cessation
≥20mg / day ≥14 days 1 month before or at least 1 month after
cessation
Corticosteroids and Live Vaccines
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Corticosteroids and DMARDS
If on <20mg prednisolone equivalent daily and low dose DMARDS then can still receive live vaccines
Low dose DMARDS:Drug Dose in 70kg adult
Methotrexate ≤0.4mg/kg/week = 28mg
Azathioprine ≤3mg/kg/day = 210mg
Mercaptopurine ≤1.5mg/kg/day= 105mg
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Recent Blood Products /
Immunoglobulins
BCG, Zoster and Yellow Fever vaccination can be given any time before or after
blood products
Product Interval Before Live (MMR, MMRV, Varicella) Vaccination
Blood transfusion / washed RBCs 0 months
RBCs 3 months
Packed RBCs 5 months
Whole blood 6 months
NHIG for ITP / KawasakiNHIG for measles / hepA prophylaxis
8-11 months3-6 months
Plasma or platelets 7 months
RhD Ig (anti-D) 0 months
ZIG as varicella prophylaxis 5 months
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HIV Infection
Live vaccines o Contraindicated if CD4 <200/μL (<15%), history of AIDS-defining illness, symptomatic HIV
infection
o BCG is always contraindicated
o Can give YF, MMR (if seronegative) and VZV (if seronegative) vaccines but NOT combined MMRV in asymptomatic HIV infection and those with CD4 ≥200/μL (15%)
o Zoster vaccine if ≥ 50 years and VZV IgG+ and CD4 ≥350/μL (some say ≥200/μL safe)
Inactivated Vaccineso Annual influenza
o Pneumococcal vaccination (1 x PCV13 + 2x PPV23)
o 4vMenCV and MenB – 2 doses of each
o HepA if non-immune
o HepB 4 double doses at 0, 1, 2 and 6m more immunogenic, check anti-HBs and repeat doses if <10mIU/mL
o 4vHPV – 3 doses @ 0, 2 and 6m. Females <45 yrs and males <26 yrs as per guidelines
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Asplenia
At risk of fulminant bacterial infection particularly invasive pneumococcal disease
Go to Spleen Australia website for up-to-date advice https://spleen.org.au
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Immunocompromised Travellers
o Yellow fever vaccine should be avoided in severe immunocompromise (travellers may need an exemption certificate)
o Do not give BCG
o Use the inactivated typhoid Vi polysaccharide vaccine not the live oral vaccine
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Household Contacts
Vaccinate household & close contacts of
immune compromised
persons according to current
recommendations
In particular annual influenza
vaccination
Use of live vaccines in
contacts is highly recommended
Consider need for VZV (if ≥50
years) and pertussis-containing vaccines
Small risk of rotavirus vaccine
virus transmission to
the immune compromised
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Name Target
Bimagrumab Type II activinrecptors
Alirocumab PCSK-9
Bocociziumab PCSK9
MABp1, Xilonix IL-1α
Gevokizumab IL-1β
Dupilumab IL-4Rα
Reslizumab IL-5
Benralizumab IL-5R
Sirukumab IL-6
Sarilumab /SA237 IL-6R subunit α
Lebrikizumab / Tralokinumab IL-13
Ixekizumab IL-17a
Brodalumab IL-17R
Tildrakizumab / Guselkumab IL-23 p19 subunit
Name Target
Actoxumab + Bezlotoxumab C diff enterotoxin A & B
Etrolizumab β7 integrin subunit
Tremelimumab CTLA4
MM-302 HER2
Patritumab HER3
MEDI-4736 / RG7446,MPDL3280A
PD-L1
Elotuzumab CD2
Inotuzumab ozogamicin / Moxetumomeb pasudotoc
CD22
Daratumumab CD38
Eculizumab Anti-complement C5
Rituximab / Ocrelizumab CD20
Alemtuzumab CD52
Epratuzumab CD22
Immunotherapies
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Rituximab
o Depletes B cells (anti-CD20)
therefore prevents antibody
responses
o Different studies show differing
effects but generally vaccine Ab
responses (and CMI) impaired for up
to 6 months post administration
o Preferable to vaccinate prior to
commencing therapy if possible
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Eculizumabo Indications: paroxysmal nocturnal
haemoglobinuria and atypical haemolytic uraemic syndrome
o Worlds most expensive drug, 2010 (£340,000/dose but now about $6,000)
o Associated with increased susceptibility to serious Neisseria meningitidis infection with a rate of 1% (Australian average rate: 1/100,000)
o Meningococcal vaccination recommended before starting treatment 4vMenV and MenBV 2 doses 8 weeks apart then check titres for response
o Check Ab titres annually if ongoing therapy and revaccinate if titres fall
o Antibiotic prophylaxis (PenV / erythromycn) also indicated
Prevents formation of the terminal complement complex C5b-9, by inhibiting the cleavage of C5-C5a
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Immune Checkpoint Inhibitors
& Flu Vaccination
Influenza vaccination has been associated with increased incidents of myocarditis and death in people on checkpoint inhibitors
One study showed PD-1/PD-L1 inhibs caused >50% immune related AEs (rash, arthritis, encephalitis, colitis) (>25% had severe irAEs)
Australian immunisation handbook says to consult your oncologist for advice
They are likely to ask the ID physician / local vaccination specialist
Trials are ongoing to investigate this systematically
Pembrolizumab (PD-1 inhibitor), Nivolumab (PD-1 inhibitor) Atezolizumab (PD-L1 inhibitor), Ipilimumab (CTLA4 inhibitor)
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Immune Checkpoint Inhibitors & Flu Vaccination
Can give if on single agent aPD-
1 or aPD-L1
Do not give flu vaccine within
6-8 wks of starting CTLA4 inhibs / combo therapy or 6-8
wks of stopping
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Thank You