Transcript Vaccination of the Immune Compromised Host

Vaccination of the Immune
Compromised Host
Wales 2008
D Baxter
Vaccination of the Immune
Compromised Host
Wales 2008
Primary and
Secondary IDs
http://www.wadsworth.org/chemheme/heme/microscope/pix/spherocytes_nw.jpg, http://www.immunedisease.com/US/images/IDF9.jpg,
http://www.omsusa.org/immuneglobulin.jpg, http://blog.joins.com/usr/d/r/drsuekim/19/SCID_patient.gif,
http://www.foxnews.com/images/263519/2_61_tiny_baby1.jpg, http://geraldofreire.uol.com.br/jane_fonda.jpg,
http://www.niaid.nih.gov/daids/dtpdb/graphics/hiv.gif, http://www.pearlgrimesmd.com/images/bavit2.jpg
http://library.thinkquest.org/03oct/01254/images/immune_map.jpg
Innate
response
Recognised by APCs, Complement (C3b), Acute
phase proteins (eg CRP). Inflammatory response
initiated by cytokines (Il-1, IL-6, TNF)
Sentry
Function
Initial response –
acute inflammation
Adaptive
response
initiated by
APCs
Defects in the immune system are collectively termed “immunodeficiency
disorders”. They may involve the innate, adaptive systems or external/
physiological barriers. They may be primary or secondary disorders. There
are also situations where the immune response may be impaired, but not
classically immunodeficient.
Primary Immunodeficiency Disorders
• Data on PID frequency vary: in Australia the
prevalence of PID is estimated at 1:36,000 – for
both Switzerland and Norway the comparable
figure is 1 in 14,000. In the US, the prevalence is
estimated at between 1 in 5000 – 10,000
• A meta-analysis using immunodeficiency registers
from Spain, Australia, Norway and Latin America
found that defects in the innate system made up
10% of cases with adaptive system defects
causing 90% of cases.
Hereditary Spherocytosis
Ms A was an 18 year patient who had
HS – as did her mother and brother.
The patient had several aplastic crises
which were managed conservatively.
Haemolysis in HS results from the
interplay of an intact spleen and an
intrinsic membrane protein defect that
leads to abnormal RBC morphology. HS
erythrocytes are caused by membrane
protein defects resulting in cytoskeleton
instability.
However, she subsequently developed
anaemia and had an elective splenectomy.
Whilst this proved an effective treatment the
absence of her spleen led to a secondary
immune deficiency disorder which put her at
risk of a number of infections and required
managing.
Pathophysiology
Macrophage and neutrophil chemotaxis is
reduced and phagocytic inactivation of
bacteria is reduced in neutrophils. The
introduction of billions of organisms IV leads to
their clearance from blood in three passes
through the spleen.
http://www.udel.edu/biology/Wags/histopage/illuspage/ilst/ilst.htm,
http://uhaweb.hartford.edu/BUGL/immune.htm,
http://library.thinkquest.org/03oct/01254/images/immune_map.jpg,
Alberio and Lämmle 339 (25): 1827, Figure 1
December 17, 1998 NEJM
Post-splenectomy infection risk
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Asplenia or splenic hypofunction
predisposes individuals to risk of
overwhelming infection.
These infections are most often due to
encapsulated organisms, especially S
pneumoniae, Haemophilus influenzae type
b, and N meningitidis, but any bacterial
agent may cause the rapid onset of
septicemia, meningitis, pneumonia, and
shock characteristic of the asplenichyposplenic condition - OPSI. [influenza/
capnocytophaga]
The risk is greatest in infants and young
children, but asplenic-hyposplenic adults
also have an increased risk of infection.
Education about risk, prophylactic
antibiotics and pneumococcal immunisation
(Hib/ Men C) have reduced the incidence of
infections in asplenic-hyposplenic
individuals, but even these measures have
not eliminated the risk.
Surgical procedures designed to maintain
some splenic function have been
implemented but these have not provided
total protection against overwhelming
infection.
Infection risk following splenectomy is
influenced by the the underlying disease
or condition leading to splenectomy.
Splenectomy incidental to other
operations, such as gastrectomy, results
in the lowest risk for overwhelming
infection, but this is still some 35-fold
greater than the risk for overwhelming
infections in the general population.
In increasing order of risk, the other
main indications for surgical removal of
the spleen are idiopathic
thrombocytopenia purpura, trauma,
transplantation procedures, hereditary
spherocytosis (350 fold increase in risk),
staging Hodgkin's disease, portal
hypertension with hypersplenism, and
thalassemia.
Risk is highest in the first 2 years
following splenectomy but very late
sepsis has been described at a rate of
0.69 cases of sepsis or meningitis in
1000 patient-years (0.46 deaths in 1000
patient-years).
Questions to consider
• How serious are pneumococcal , meningococcal, H
influenzae, capnocytophagus, malaria and flu in a
splenectomised individual?
• How good are pneumococcal , meningococcal, H
influenzae, and flu vaccine in a splenectomised
individual?
• Are there any side effects to pneumococcal ,
meningococcal, H influenzae, and flu vaccine in a
splenectomised individual?
• What are the particular contra-indications to
pneumococcal , meningococcal, H influenzae, and flu
vaccine? (Manufacturer/ any other authoritative group)?
• Is there any other way(s) of controlling pneumococcal ,
meningococcal, H influenzae, and flu vaccine in a
splenectomised individual?
Post-splenectomy vaccine management
• Pneumococcal vaccine
• Meningococcal vaccine
• Haemophilus influenza b
• Influenza vaccine
• Antibiotics/ malaria advice /capnocytophagus
Classification of Primary Immunodeficiency Disorders
System involved
Cell/ component
Disorder
Subtype
Phagocyte (8%)
Primary Neutropenia
Kostmann’s disease
Other
Leucocyte Adhesion Defect
LAF-1 deficiency
Sialyl Lewis X deficiency
Innate
Chediak-Higashi syndrome
Chronic Granulomatous disease
X-linked
Autosomal
Immunodeficiency with partial
Albinism
Congenital Asplenia
Complement (2%)
Complement deficiencies
C1q, C1r, C1s
C2, C3, C4, C5, C6, C7,
C8, C9,
Properdin, Factor B
Factor D,
C1-esterase inhibitor
deficiency
C3b-inactivator deficiency
Questions
Pneumococcal Invasive Disease
• Patient B presented at 33
years of age with confirmed
pneumococcal meningitis.
• In their previous history, they
had had an astrocytoma
removed with radiotherapy
and chemotherapy.
• There was no history of
recurrent infections,
eczema, or diarrhoea
• Seen in clinic because of
“invasive pneumococcal
disease”
http://www.lifespan.org/adam/graphics/images/en/2930.jpg
http://library.thinkquest.org/03oct/01254/images/immune_map.jpg
Innate
response
Recognised by APCs, Complement (C3b), Acute
phase proteins (eg CRP). Inflammatory response
initiated by cytokines (Il-1, IL-6, TNF)
Sentry
Function
Initial response –
acute inflammation
Adaptive
response
initiated by
APCs
Antibody Deficiency
IgG1. This is the most
abundant subclass:
recognises protein antigens
- important in fighting viral
infections.
IgG2. This is the second
highest subclass in
concentration. It neutralises
infections caused by
bacteria with
polysaccharide capsules.
IgG3. This is present in
smaller quantities, and has
a similar function to IgG1.
IgG4. Normal
concentrations of this
subclass can be very low functional role not known.
Copied from Ron L and Benhur Lee,
http://www.pia.org.uk/publications/general_publications/i
gg_subclass_deficiency.htm#whatare
Pneumococcal Invasive Disease
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Patient B presented at 33 years of age
with confirmed pneumococcal
meningitis.
In their previous history, they had had
an astrocytoma removed with
radiotherapy and chemotherapy.
There was no history of recurrent
infections, eczema, or diarrhoea
Seen in clinic because of “invasive
pneumococcal disease”
FBC and differential normal
IgG 5.2 (5.9-15.6) g/L
IgA 0.4 (0.6-5.0) g/L
IgM 0.3 (0.1-3.6) g/L
Tetanus antibodies 0.78 iu/ml
Serotype specific Pneumococcal
antibodies 0.01μg/ml (>0.35 μg/ml)
Probable diagnosis Common Variable
Immune Deficiency
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CVID can become evident at any time
from infancy to after the fourth decade
of life.
Peaks of onset occur in children aged
1-5 years and in persons aged 16-20
years.
More than two thirds of patients are
aged 21 years or older when CVID is
diagnosed.
25% are autosomal dominant
Barrier Effect
Nasal turbinates/branching tracts
Antimicrobial molecules (including stratum
corneum lipids)
Shedding of skin/peristalsis/tears/urine
Commensals
Dry skin surface +low pH
Adaptive
Antibody (73%)
Agammaglobulinaemia
X-linked
Autosomal recessive
Sporadic
Common Variable Immunodeficiency
(50%): 1 in 50,000/200,000 – [IgG, IgA,
IgM] {IgG & IgA}
Associated with thymoma
Associated with transcobolamine II
deficiency
Hyper IgM syndrome
X-linked
Autosomal recessive
Sporadic
Immunoglobulin class deficiency (IgA 30%)
Associated with IgG subclass
deficiency
Immunoglobulin subclass deficiency
IgG subclass
IgA subclass
Associated with gene deletion
Immunoglobulin light chain deficiency
Deficiency of specific Antibody
Questions to consider
• How serious is H influenzae, S pneumoniae,
staphylococci, Moraxella, Mycoplasma pneumonia and
G lamblia in the individual with CVID?
• How good (effective/ immunogenic) is the particular
vaccine in the individual with CVID?
• Are there any side effects to the particular vaccine in the
individual with CVID?
• What are the particular vaccine contra-indications
(Manufacturer/ any other authoritative group)?
• Is there any other way(s) of controlling the particular
disease in the individual with CVID?
CVID vaccine management
• There is no consensus on the role of
active immunity (Toxoid, subunit, killed/
inactivated).
• Administer passive immunity (Tetanus,
Hepatitis B and Rabies) as appropriate
• No live vaccines (MMR, BCG, YF)
• Education/ diet (risk of infection),
Immunoglobulin, antibiotics
Questions
Patient C
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Patient C was referred to clinic at
10 months of age with an abscess
at the site of their 3rd
immunisation. The abscess was
drained. However, there was a
history of weight loss, recurrent
infections and failure to thrive. The
child was transferred to the
Regional Immunology Unit with a
diagnosis of T+B+ SCID X-linked.
At 11 months of age the child had
a haploidentical paternal T cell
depleted BMT.
The child was put on penicillin
prophylaxis.
The child has subsequently been
immunised effectively.
T cell or combined (T and B cell)
deficiencies 17%
Absence of T cells with normal or increased B cells
(SCID – all forms 4%)
Autosomal recessive SCID
Other forms of SCID
T cell receptor deficiency
Di George anomaly
Ataxia telangiectasia
Other chromosomal breakage syndrome
Deficiency of HLA expression
Adenosine deaminase deficiency
Purine nucleoside phosphorylase deficiency
Wiskott Aldrich syndrome
Omenn’s syndrome
Reticular dysgenesis
Short limbed dwarfism
Chronic mucocutaneous candidiasis
X-linked severe combined
immunodeficiency (IL2 receptor γ chain
deficiency)
Autosomal recessive
Sporadic
Immunosuppressive drugs
• Ms Y is a 45 year old lady who
had breast conserving surgery
for Ca breast: she
subsequently receives
radiotherapy and systemic
chemotherapy with
cyclophosphamide,
methotrexate and 5-FU (5
Flurouracil). She wanted to
travel on a round the world trip
and required tetanus,
diphtheria, polio, rabies,
meningococcal vaccine,
influenza and yellow fever.
How to advise?
Immuno-suppressive drugs
• Cyclophosphamide - a synthetic alkylating agent
chemically related to the nitrogen mustards with
antineoplastic and immunosuppressive activities.
• Methotrexate - an antimetabolite with antineoplastic and
immunomodulating properties.
• 5 fluorouracil - an antimetabolite fluoropyrimidine analog
of the nucleoside pyrimidine with antineoplastic activity.
• Do not have live vaccines during treatment or for 6
months after completion of treatment.
• Subunit, inactivated/ killed or toxoid vaccines can be
given but they may be less effective
Questions
Immune Impaired
• Baby D was born at
25 weeks gestation –
she was on SCBU
where she was
ventilated. She is 56
days old – what
immunisations should
she receive and how
will she respond to
them?
Prematurity
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One in 13 live births in England and
Wales are preterm: of these 7% of are
born prior to 28 weeks and this figure
may be increasing.
Preterm and low birth weight infants
are at increased risk of infections
including vaccine preventable illness.
Vaccination is more likely to be
delayed in pre-term infants and there
are concerns, about whether
vaccination will stimulate adequate
antibody responses particularly among
very premature infants (<30 weeks of
gestation).
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Stockport Specialist Immunisation Clinic
131 preterm infants born at Stepping Hill
Hospital between June 1998 and November
2005.
UK routine primary vaccinations were given
at 2, 3 and 4 months chronological age.
Pneumococcal conjugate vaccine (PCV) for
at risk children was given at 10, 14 and 18
weeks.
Antibody titres 4 weeks after the last primary
dose
A protective immune response was
developed by 76.5% of preterm infants
against diphtheria (95% Confidence Interval
(CI) 68.8-84.3), by 86.6% against Men C (CI
80.4 – 92.7) and by 98.3% against tetanus
(CI 96.1 – 100). Only 67.8% (CI 59.4-76.1)
achieved a PRP ≥0.15g/ml against
Haemophilus influenzae type b (Hib) with
only a third (34.7%) reaching ≥1g/ml. Over
half, 67.5% (CI 53.0-82.0), achieved
protective levels against pneumococcal
serogroup 6B. There was a statistically
significant inverse relationship between
gestational age and antibody titres for
diphtheria (p< 0.01) and a similar but non
significant association for tetanus (p<0.06).
Baxter, Gebrehewet, Welfare, Dao
Questions to consider
• How serious is the particular disease(s) in the individual
with the specified immune deficiency disorder?
• How good (effective/ immunogenic) is the particular
vaccine in the individual with the specified immune
deficiency disorder?
• Are there any side effects to the particular vaccine in the
individual with the specified immune deficiency disorder?
• What are the particular vaccine contra-indications
(Manufacturer/ any other authoritative group)?
• Is there any other way(s) of controlling the particular
disease in the individual with the specified immune
deficiency disorder?
General Principles
• Killed or inactivated vaccines do not represent a danger
to immunocompromised persons and generally should
be administered as recommended for healthy persons.
• For specific immunocompromising conditions (e.g.,
asplenia), such patients may be at higher risk for certain
diseases, and additional vaccines, particularly bacterial
polysaccharide vaccines {Haemophilus influenzae type b
(Hib), pneumococcal and meningococcal}, are
recommended for them.
• Frequently, the immune response of
immunocompromised persons to these vaccine antigens
is not as good as that of immunocompetent persons;
higher doses or more frequent boosters may be
required, although even with these modifications, the
immune response may be suboptimal.
• Discuss patient with paediatrician, immunologist,
oncologist
The End