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Vaccination of the Immune Compromised Host. Wales 2008 D Baxter. Vaccination of the Immune Compromised Host. Wales 2008. Primary and Secondary IDs.

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slide3

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

slide4

http://library.thinkquest.org/03oct/01254/images/immune_map.jpghttp://library.thinkquest.org/03oct/01254/images/immune_map.jpg

Recognised by APCs, Complement (C3b), Acute phase proteins (eg CRP). Inflammatory response initiated by cytokines (Il-1, IL-6, TNF)

Sentry Function

Innate response

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
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
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.

slide7

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
Post-splenectomy infection risk

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).

  • 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 asplenic-hyposplenic 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.
questions to consider
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
Post-splenectomy vaccine management
  • Pneumococcal vaccine
  • Meningococcal vaccine
  • Haemophilus influenza b
  • Influenza vaccine
  • Antibiotics/ malaria advice /capnocytophagus
pneumococcal invasive disease
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

slide14

http://library.thinkquest.org/03oct/01254/images/immune_map.jpghttp://library.thinkquest.org/03oct/01254/images/immune_map.jpg

Recognised by APCs, Complement (C3b), Acute phase proteins (eg CRP). Inflammatory response initiated by cytokines (Il-1, IL-6, TNF)

Sentry Function

Innate response

Initial response – acute inflammation

Adaptive response initiated by APCs

antibody deficiency
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/igg_subclass_deficiency.htm#whatare

pneumococcal invasive disease16
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

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

Pneumococcal Invasive Disease

Barrier Effect

Nasal turbinates/branching tracts

Antimicrobial molecules (including stratum corneum lipids)

Shedding of skin/peristalsis/tears/urine

Commensals

Dry skin surface +low pH

questions to consider18
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
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
patient c
Patient C
  • 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.
immunosuppressive drugs
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
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
immune impaired
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
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).

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

Prematurity
questions to consider28
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
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