Immunomodulators Handout

8/12/2019 Immunomodulators Handout

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Immunomodulators

Immunosuppressants

ImmunostimulantsVaccines


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Lecture objectives

Recognize medications used to stimulate theimmune system

Recognize medications used to inhibit theimmune system

Define their mechanisms of action Apply the use of these medications to specific

medical conditions List their contraindication/precautions

Recognize side effects and interactions Define the current guidelines regarding

immunizations, recognize contraindications, sideeffects associated with each vaccine

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Transplantation therapy

Start with antibodies to establish graft

Muronomab CD3 and anti-CD25

or antilymphocyte antisera

Maintain with

Calcineurin inhibitor, glucocorticoids and/or

antimetabolite

Antibodies


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Therapy for organ rejection

Add to the previous medications

Anti T cell therapy (established cells)

High dose glucocorticoids

Anti T cell antibodies

Polyclonal antilymphocyte antibodies

Muromonab CD3


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Immunosuppressive medications

Glucocorticoids

Calcineurin inhibitors

Antiproliferative agents Antimetabolic agents

Antibodies


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Novel transplantation without

immunosuppression

Would involve co-transplanting donor stem

cells with the transplanted organ

Some liver transplants may contain

hematopoetic stem cells.


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IMMUNOSUPPRESSANTMEDICATIONS

Glucocorticoids

Calcinuerin inhibitors

Cyclosporin

Tacrolimus

And other agents


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Examples of corticoids

Hydrocortisone

Triamcinolone

Dexamethasone

Prednisolone

Cortisone

Aldosterone

Betamethasone

Methylprednisone


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Therapeutic uses of glucocorticoids

Replacement therapy Acute rejection Acute exacerbation of

autoimmune disease

Graft-versus-host disease Bone marrow transplants Rheumatoid arthritis Asthma, allergy SLE

Psoriasis Inflammatory bowel

disease

Nephrotic syndrome

Infectious disease,pneumonia in AIDS

Skin lesion, GI disease,

hepatic disease Malignancies, edema,

thrombocytopenia

Stroke and spinal injury,organ transplants

Multiple sclerosis .


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Mechanisms of Glucocorticoids

Lyse lymphocytes

Rapid decrease in T cell count

Down regulate cytokines IL 1 and 6

Decrease production of IL 2

Prevent proliferation of T cells

Decrease activity of neutrophils andmonocytes


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Side effects of glucocorticoids

Growth retardation

Bone necrosis

Infection

Poor wound healing

Cataracts, glaucoma

Ulcers

Hyperglycemia

Hypertension

Dependency


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Toxicity of glucocorticoids

Withdrawal of therapy

Fluid and electrolyte abnormalities

Hypertension, hyperglycemia Infections, osteoporosis, cataracts

Growth arrest

Fat redistribution


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Glucocorticoid Inhibitors

Mitotane, metyrapone, aminoglutethimide,

ketoconazole

Used in cancer therapies, cushings,..

Mifepristone


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Corticosteroids

Cortisone and prednisone must be converted toactive form by the liver

Less effective in liver disease


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Withdrawal from steroid therapy

step-down therapy

Often flare up of disease is suppressed by high

steroid dosage, twice a day

Once symptoms have subsided, consider step

down steroid therapy

Change divided dose to once daily dose

am administration


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Step down therapy

If less than 2 weeks on steroids

Combine divided dose into once daily

If greater than 2 weeks on steroids

Convert over 2 week period to single daily dose

Slowly decrease second dose, while increasing am

dose


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Alternate day therapy

Stabilize on once daily

Then step down to alternate day

Use short or intermediate acting steroid for alternate daydosing

Cortisone Hydrocortisone

Prednisone

Prednisolone

Methylprednisolone

Triamcinolone

(Long acting drugs include dexamethasone and betamethasone)


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Conversion- example

Daily mg prednisone

Minimize effective daily dose

Every other day dose should be 2.5-3 times

the daily dose

Taper off day dose by 2.5-5 mg prednisone per

week until every other day dose is reached


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Discontinuation of therapy

Variable tapers suggested

Monitor closely for flare of disease during

taper

Any stresses may require additional dose


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Recognize Withdrawal symptoms

Nausea, vomiting, anorexia

Headache, joint pain, fever

Lethargy, myalgia Hypotension

Weight loss


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Prednisone

Taper off slowly

Interactions due to being a CYP 3A3/4

substrate

Inducers like phenytoin, rifampin decrease the

effectiveness of prednisone


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OTHER IMMUNOSUPPRESANTS


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Calcineurin inhibitors

Cyclosporine and tacrolimus

Block second messenger activity

Block induction of cytokine genes Including IL2

Block T cell growth and differentiation


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Cyclosporine

Beauveria niveafungus

Highly lipophilic

Iv or oral

Used to prevent transplant rejection

Can be used in autoimmune disease


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Cyclosporine

Generics not always comparable to trade

CYP 3A4 metabolism

Adjust dose in liver dysfunction Excreted in feces

Milk


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Dosing cyclosporine

Usually with glucocorticoids and

antimetabolites

With sirolimus

Dosage depends on individual

Monitor

Rejection- increase dose

Toxicity- decrease dose


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Rheumatoid arthritis

Cyclosporine

With methotrexate and corticoids


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Toxicity of cyclosporine

Renal dysfunction

Elevated SCr (25-38%)

Tremor (12-55%)

Hirsutism

Hypertension (13-53%)

Diabetogenic

GI N/D, abdominal pain (12-23%) Infection, lymphoma, gingival hyperplasia


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Cyclosporine

Increase plasma levels of

Digoxin, methotrexate, simvistatin, atorvastatin,

Requires close monitoring of these meds


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Cyclosporine

DO NOT substitute

Oral Sandimmune for

Neoral, Gengraf or modified cyclosporine oral

Sandimmune is less bioavailable

Neoral=Gengraf=modified oral Cyclosporine


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Novel uses of cyclosporine

Immunosuppression in early stages of type 1

diabetes

May delay insulin requirement in some

patients


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Tacrolimus

Macrolide antibiotic

Streptomyces tsukubaensis

Calcineurin inhibitor at a different site from

cyclosporine

Oral or injection

Require careful individualization of therapy Binds plasma protein, metabolized by 3A4


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Therapeutic uses

Prophylaxis of organ transplant

Rescue of acute rejection


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Toxicity of tacrolimus

Nephrotoxic

Neurotoxic

GI, hypertension

Hyperkalemia, hyperglycemia and diabetes

Risk of tumors and secondary infection

Headache, fever, skin burning, pruritis,erythema, cough, flu-like effects

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Interactions

Monitor for toxicity

Renal function and blood levels

Additive toxicity with cyclosporine

Many possible interactions through 3A4

Separate antacids by 2 hours



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Anti-proliferative agents

Sirolimus (rapamycin, Rapamune)

Streptomyces hygroscopicus

Inhibitor of T cell activation and proliferation

Different site from cyclosporine and

tacrolimus



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Therapeutic uses

Prophylaxis of organ transplant

Used with glucocorticoid and calcineurin

inhibitor

Can be used with glucocorticoid and anti-

metabolite in renal dysfunction

Use with prophylactic treatment for

Pneumocystis cariniiand cytomegalovirus



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Toxicity

More lymphocoele with sirolimus

Renal toxicity with cyclosporine

Anemia, leukopenia, thrombocytopenia

Hypo or hyperkalemia

Fever and GI distress

Cancer risk, infections



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Interactions

Numerous through CYP 3A4

Through P glycoprotein binding in serum

Cyclosporine and sirolimus interact

Separate administration by 24 hours

Monitor blood levels closely



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ANTI-METABOLIC AGENTS

Azathioprine

Mycophenolate mofetil

Methotrexate

Cyclophosphamide.Cytoxan

Chlorambucil/Leukeran

Leflunomide/Arava



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Methotrexate

Mostly renal metabolism (90%)

Toxicities at low dose include

Mucositis, acute elevation of liver enzyme

N/V/D

Monitor

LFTs

24 hour post dose level is detectable, may giveleukovorin rescue



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Methotrexate

Interactions

Increased toxicity by addition of

Cyclosporine, sulfonamides, high dose penicillins,

ethanol, salicylates

Methotrexate may increase cyclosporine

plasma levels and toxicity



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Treatment of methotrexate OD

Glucarpidase /VORAXAZE

Carboxypeptidase



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Azathioprine/Imuran

Purine antimetabolite

Glutathione needed to convert to 6

mercaptopurine

Inhibitor purine synthesis

Inhibits cell proliferation

Taken orally



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Therapeutic use of azathioprine

Kidney transplant

Prevention of rejection

Severe rheumatoid arthritis



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Interactions

Allopurinol

Reduce dose of azathioprine

Care with ACE inhibitors



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Mycophenolate mofetil/Cellcept

Inhibitor of guanine synthesis

Decreases proliferation of T and B cells

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Mycophenolate

Toxicities >10%

Hypertension, cardiac, CNS (pain, headache,

insomnia, tremor) dermatological, hyperglycemia,

electrolyte imbalances, abdominal pain, diarrhea,nausea, constipation, TUI, neutropenia,

neurological, pulmonary, renal

Infections, bacterial, fungal and viral


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Mycophenolate

Interactions

Antacids with aluminum or magnesium

Acyclovir, ganciclovir


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ANTIBODIES

Antithymocyte globulin

Muromonab CD3

Humanized anti CD3

Anti IL 2 receptor antiobies

Infliximab/Remicade

Etenercept/Enbrel


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Antibodies

Anti lymphocytes

Anti cell surface antigen

Poly and monoclonal

Control of polyclonal quality difficult


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Antithymocyte


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Antithymocyte

globulin/Thymoglobulin

Rabbit gamma globulin

Anti human thymocyte

Used iv

Depletes human T lymphocytes

Used in induction at time of transplantation

Also acute rejection


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Toxicity

Immune reponse

Fever and chills

Hypotension

Can take with glucocorticoids to reduce effects

Serum sickness and glomerulonephritis

Rare anaphylaxis

Infection and cancer


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Anti CD3 (muromonab CD3)

Monoclonal mouse antibodies

Reverses acute rejection

iv

T cells decrease within minutes

Return 1 week after therapy

Immunizes patient, limits use


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New generation CD3 ab

Genetically altered

Humanize to reduce reactivity to constant

regions

Less toxicity


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Anti IL2 receptor antibodies

Daclizumab/Zenapax

Basiliximab/Simulect

Humanized mouse chimera

Human constant region IgG1 attached to

mouse variable domains

Used in acute rejection

No cytokine release syndrome


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Infliximab/remicade

Chimeric and TNF awith human constant

region

Used in inflammatory disorders

Crohns, arthritis

Causes inflammatory reactions

Fever, hypotension, infections, lupus


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Etanercept/Enbrel

Fusion protein TNFareceptor to Fc human

IgG1

Binds TNF aand inhibits receptor binding

Used in rheumatoid arthritis

Can cause inflammatory response


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Alefacept

AMEVIVE Immunosuppressant

Dimeric fusion protein extracellular CD2 receptor ofhuman leukocyte antigen 3 linked to Fc region of

human IgG1 Used in psoriasis

Adverse reaction Lymphopenia

Malignancies Serious Infections requiring hospitalization

Hypersensitivity Reactions


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TREATMENT WITH IMMUNESUPPRESSANTS


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Typical treatment

Primary

Methylprednisomone

Cyclosporine

Tacrolimus

Antithymocyte globulin

Prophylaxis of infectious diseases


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FUTURE DIRECTIONS IN ORGANTRANSPLANTATION


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Co-transplant bone marrow

HLA-mismatched renal transplantation

Plus bone marrow transplantation

Successfully wean some patients off all

immunosuppressants

NEJM 2008, 358:407.


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Immunostimulation


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Immunostimulation

Levamisole/Ergamisol

Thalidomide

Bacillus Calmett-Guerin (BCG)/Therasys

Interferons (a,band g)

Interleukin 2/Proleukin


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Thalidomide

Restricted distibution

Erythema nodosum leprosum

Decreases TNF ain leprosy

Increase TNF ain HIV

May be useful in rheumatoid arthritis


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/ l d


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LENALIDOMIDE/Revlimid

Thalidomide derivative

BBW

Pregnancy

Blood clot

Indications

Multiple myeloma

Myelodysplactic disorders


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Bacillus Calmett-Guerin


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Bacillus Calmett Guerin

(BCG)/Therasys

Attenuated, live culture

Mycobacterium bovis

Used in carcinoma in situ

Bladder and papillary tumors

Mechanism unclear


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I f ( b d )


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Interferons (a,band g)

Anti-viral

Immunostimulant


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I f 2b


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Interferon a2b

a2b genetically engineered E.coli

Tumors

Malignant melanoma, hairy cell leukemia,

Kaposis

Infectious disease, hepatitis B and C


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I f 1b/A i


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Interferon gamma 1b/Actimmune

Activates phagocytes

Reduces frequency and severity of chronic

granulomatous infections


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I f b 1 /A B


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Interferon b1a/Avonex, Betaseron

Antiviral

Relapsing and relapsing-remitting multiple

sclerosis


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I t f id ff t


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Interferon side effects

Fever, headache, rash,

Flu like symptoms

acan cause cardiovascular problems

Hypotension, arrhythmias, cardiomyopathy, MI


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I t l ki 2/P l ki


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Interleukin 2/Proleukin

Enhances lymphocyte proliferation

Increases cytotoxicity and killer cell activity

Used in metastatic renal cell carcinoma

Melanoma

Can cause severe cardiovascular toxicity


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T t t f RSV


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Treatment for RSV

Palivizumab

Humanized moAb

Indicated for at risk children

15 mg/kg administered prior to RSV season or

before bypass operations

Adverse effects

Anaphylaxis and URI possible

Preg C


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L t bj ti


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Lecture objectives

To gain an understanding of current vaccinationpractices

Describe basis of vaccination as public health carepolicy

Differentiate between live attenuated and killedvaccines, and indications for both

List the most common vaccinations andrecommendations regarding their use

Describe emerging diseases and discuss optionsfor protecting the populations at risk


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Attributes of useful vaccination


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Attributes of useful vaccination

Antigen must NOT be infective

Must elicit appropriate immune response for

this infectious agent

Cell mediated or antibody

Long-term protection

Often requires boosters

Stable and inexpensive

Easy to deliver


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Types of vaccines


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yp

Live vs killed vs genetically engineered Vaccines are available for

Hepatitis B virus Hepatitis A virus Haemophilus Influenza Diptheria Pertussis Tetanus Measles Mumps Rubella Polio Rabies Yellow fever Varicella zoster Smallpox Anthrax H1N1 Rotavirus


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Live attenuated organisms


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Live attenuated organisms

Live attenuated organisms Organisms cultured to mutate to less pathologic form

Good cell mediated immune responses

Often, only a single dose is needed to induce long term immunity.

Cheap

Potential drawbacks

Possible reversion to virulence May cause serious disease in immunocompromised individuals

Poor stability.

Heterologous vaccines Closely related organism of lesser virulence

vaccinia virus: Both cowpox virus and vaccinia virus are closely related to

variola virus Live recombinant vaccines

genetic engineering


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Killed (inactive) vaccines


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Grow bulk organism in vitro Inactivate with either beta-propiolactone or formaldehyde

Subcellular fractions

Selected purified proteins of an organism

fewer local reactions occur at the injection site.

poor immunogenicity, multiple boosters.

Recombinant proteins Grow antigen in genetically engineered organisms such as Ecoli or

yeast.

Extract antigen for use May have some sensitivity issues with the non-infectious organism


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Immune response

poor; only antibody - no cell immediated immune response.

response is short-lived and multiple doses are needed.

may be enhanced by the incorporation of adjuvants into the vaccine preparation

Safety Inactivated, therefore cannot replicate in the host and cause disease.

Local reactions at the site of injection may occur. Stability

Efficacy of the vaccine does not rely on the viability of the organisms.

These vaccines tend to be able to withstand more adverse storage conditions.

Expense Expensive to prepare.


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Adjuvants


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Adjuvants

Certain substances, when administered simultaneously with a specific antigen, willenhance the immune response to that antigen. Such compounds are routinelyincluded in inactivated or purified antigen vaccines. Adjuvants in common use:

Aluminium salts First safe and effective compound to be used in human vaccines.

It promotes a good antibody response, but poor cell mediated immunity.

Liposomes and Immunostimulating complexes(ISCOMS)

Complete Freunds adjuvantis an emulsion of Mycobacteria, oil and water Too toxic for man

Induces a good cell mediated immune response.

Incomplete Freund's adjuvantas above, but without Mycobacteria.

Muramyl di-peptide Derived from Mycobacterial cell wall.

Cytokines IL-2, IL-12 and Interferon-gamma.


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PASSIVE IMMUNIZATION

Rhogam


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Medicine 99

Rhogam

Rho(D)

Erythroblastosis fetalis

Given to Rh mothers if father is Rh+

One shot at 7 months gestation

One at parturition

Protects subsequent pregnancies


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SMALL POX


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Small pox vaccine


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Small pox vaccine

First vaccinations Used pus from existing infected individual

Jenner used cowpox as successful vaccination

Currently eradicated

Available vaccine

Live attenuated

3-5 year immunity


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Small pox vaccine


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Small pox vaccine

Not for children under 12 months

Not for pregnant women

Not for immunocompromised or on

immunosuppressive medication

People with previous skin conditions are at

greater risk of serious side effects

Heart conditions and diabetes also


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MMR


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Measles

Respiratory infection

with high fever

Skin rash


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Measles vaccine


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Measles vaccine

Vaccine first introduced in 1960s

Live attenuated virus grown in chick embryo

fibroblasts

Periodic outbreaks in previously vaccinatedcollege students.

Administered at 12 months in MMR

Booster at 11-12 years.


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Mumps


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Mumps febrile illness

swollen salivary glands Lasts about a week spread by the respiratory route 21 days incubation period. Aseptic meningitiscommon complication

Mumps meningoencephalitisis rarer but a more serious. Orchitiscan occur, more often after puberty, unilateral or

bilateral, but is rarely followed by infertility. Other glandulartissue is very occasionally involved pancreatitis, oophoritis orthyroiditis.

Diagnosis can be confirmed by positive IgM antibodies. In

cases of meningitis the virus is readily isolated from cerebro-spinal fluid.


Medicine109

Mumps vaccine


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Mumps vaccine

Live attenuated virus developed in the

1960's.

administered with measles and rubella at 12-15 months in the MMR vaccine.


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Rubella

Respiratory transmission 2-3 week incubation Rash begins behind ears and on

face, spreads Congenital rubella syndrome infection of the mother in the first

12 weeks of pregnancy 80% risk of congenital

abnormalities Specific features of congenital

rubella syndrome are: cataracts,micropthalmia, heart defects,sensorineural deafness, mental

retardation. Infection betweenabout the 13th and the 17th weekof pregnancy may result indeafness alone, but infectionbeyond the 17th week is no longera hazard.


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MMR vaccine


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MMR vaccine

Contraindications Any previous serious hypersensitivity to vaccine

Pregnancy

Known severe immunodeficiency (e.g., hematologic and

solid tumors; congenital immunodeficiency; long-term

immunosuppressive therapy or severely symptomatic

human immunodeficiency virus [HIV] infection)

Precaution

Moderate or severe acute illness


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MMR vaccine


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MMR vaccine

Common Side Effects: Seen 7 to 10 days after vaccination

Low grade fever lasting 2 to 3 days

Faint red rash (not infectious)

Head cold and/or runny nose

Cough and/or puffy eyes

Drowsiness or tiredness

Swelling of the salivary glands

A temporary small lump at the injection site

Serious Side Effects: Encephalitis (inflammation of the brain) at a rate of 1 in 1 million

Thrombocytopenia (bruising or bleeding) at a rate of 1 in 30,500 doses

Extremely Rare Side Effect: Severe allergic reaction


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POLIO


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Polio

All polio in US is currentlyvaccine related (up to 16cases per year)

Virus lives in gut, spreadsthrough oral-fecal route,particularly in swimmingpools.

Virus infects neurons,

causing paralysis ofdifferent muscles

Post-polio syndrome


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Polio vaccines


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Polio vaccines

The killed virus vaccine(Salk, 1954) (IPV) Formalin killed, grown in cultured monkey COS cells

Requires multiple boosters

Virus still replicates in gut, does not infect immunized

The live attenuated oral polio vaccine (Sabin, 1957) (OPV) Mutated, grows in gut but does not infect neurons

Better immunity, fewer boosters May mutate in gut to virulent form

Spreads to unvaccinated population

low cost

The inactivated Salk vaccine is recommended for children who areimmunosuppressed.

Adminstered at ages 2 months, 4 months, 6-18 months, and 4-6 years


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Polio vaccines


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Polio vaccines

Contraindications-Severe allergic reaction to previous dose or

vaccine component

Precautions-Pregnancy

-Moderate or severe acute illness with or

without fever


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Hepatitis B


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Hepatitis B

Clinical FeaturesIncubation period 2 - 5 months

Pathogenesisparenterally transmitted. Blood highly infections

Complications1) Persistant infection:-5% become persistantly infected.

Chronic infectionmay take one of two forms:Chronic persistent Hepatitis- the virus persists, minimal liver damageChronic Active Hepatitis- cirrhosis or liver failure.

2) Patients who become persistently infected are at risk of developinghepatocellular carcinoma (HCC)..3) Fulminant Hepatitis1% of infections

Hep B globulin available for needlestick injuries


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Hep B vaccine


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Hep B vaccine


vaccine component

Precautions

-Infant weighing < 2,000 grams


without fever


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Hepatitis A - "Infectious Hepatitis"


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p p

Clinical FeaturesIncubation period 3-5 weeks (mean 28 days)Milder disease than Hepatitis B; asymptomatic infections are very common, especially inchildren.Adults, especially pregnant women, may develop more severe disease.Although convalescence may be prolonged, there isno chronic form of the disease.

Complications:Fulminant hepatitis is rare: 0.1% of cases

Viraemia is transient.Virus is excreted in the stools for two weeks preceding the onset ofsymptoms.

Transmission - EntericLarge numbers of virus particles are excreted in stools, before the onset of symptoms. Case-to-case, via fecal-oral route.

Contamination of food or water with sewage

Infected food handlers

Shell fish grown in sewage-polluted water

DiagnosisVirus cannot be cultured in vitrofrom clinical material, and diagnosis is made on thepresence of HAV-specific IgM in the patient's blood.


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Passive immunity


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y

Normal immunoglobulin given to: Travelers to third world countries

Household contacts of acute cases


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Hepatitis A vaccine


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p

formalin-inactivated, cell culture-derived

virus.

Two doses, administered one month apart,

The vaccine is recommended for travellers to

third world countries.


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Hep A side effects


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p

soreness at the injection site (56%), headache(14%), and malaise (7), feeding problems (8%),

headache (4%), and injection-site induration

(4%).


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Hep A vaccine


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p


vaccine component

Precautions

-Pregnancy


without fever


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DTP

DiphtheriaPertussis

Tetanus


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DTaP


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Contraindications-Severe allergic reaction after a previous dose or to a vaccine component-Encephalopathy (e.g., coma, decreased level of consciousness; prolongedseizures) within 7 days of administration of previous dose of DTP or DTaP-Progressive neurologic disorder, including infantile spasms, uncontrolledepilepsy, progressive encephalopathy; defer DTaP until neurologic statusclarified and stabilized.

Precautions-Fever of >40.5 C


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,

Contraindications-Severe allergic reaction after a previous doseor to a vaccine component

Precautions-Guillain-Barr syndrome


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YELLOW FEVER


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Yellow Fever vaccine


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live attenuated vaccine

developed in 1937

administered to residents in the tropics andtravellers to endemic areas

A single dose induces protective immunity totravellers and booster doses, every 10 years,are recommended for residents in endemicareas.


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Rabies


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Cell culture derived available only Two treatment schedules

Prophylaxis Given to veterinarians and other workers who are at high risk of

exposures

2 doses, one month apart Boost after one year, then every 2-3 years

Still require additional shots after exposures

Post exposure Give after a bite from a confirmed or suspected rabid animal

Saliva is also infectious

One shot immune globulin immediately PLUS

4 intramuscular injections, as soon after the exposure as possible,then days 3, 7 and 14.


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INFLUENZA


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Influenza


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New vaccines prepared yearly

vaccines consist of partially purified envelopeproteins of inactivated current influenza A and B

strains. Who should receive vaccine

Individuals who are at risk of developing severe, lifethreatening disease if infected with influenza

Includes the elderly, immunocompromised, and patients

with cardiac disease. In these patients, protection fromdisease is only partial, but the severity of infection isreduced.


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Influenza vaccine


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vaccine component, including egg protein

Precautions


without fever


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NOVEL H1N1 INFLUENZA

Swine flu


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H1N1 vaccine


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Produced using the same methods as seasonalflu

Live attenuated intranasal vaccine

Injected killed vaccine

Two shots, one month apart, for children

under 9


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H1N1 vaccine 2009


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CDC guidelines pregnant women,

persons who live with or provide care for infants aged


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CHICKEN POX


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Varicella zoster


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Varicella zoster

This is a commonchildhood infection

mild febrile illness

generalized vesicularrash.

21 days incubationperiod.

The lesions progress from

maculeto papuletovesicleto pustuleto scab.


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Varicella zoster vaccine


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A live attenuated strain of varicella zoster virus Used to protect immune compromised

children

Required in AZ at 12 months and 2 years


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Varicella Zoster vaccine


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Contraindications-Severe allergic reaction to previous dose or vaccinecomponent-Substantial suppression of cellular immunity-Pregnancy

Precautions-Recent (


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ROTAVIRUS


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Rotarix, RotaTeq


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Live attenuated vaccine Liquid dose po

Between 6-12 weeks

2 additional doses 4 and 10 weeks later

Complete doses before 32 weeks of age

No thimerosol


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CI RotaTeq


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Immune suppression Blood disorders

Not for Fever >100C

Previous history of rotavirus Children over 2yr

Current GI illness

Failure to thrive

History of intussusception or abdominal surgery

Blood transfusion within previous 42 days Live in household with immune system compromised

individuals


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5-2010 update


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Lots of Rotarix and RotaTeq contain PCV1and/or PCV2 (porcine circovirus)

Not known to cause illness in people

Considered appropriate to continue to usethese vaccines until more information has

become available


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RECENT UPDATES


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Hemophilus influenzae type B


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January 09 Outbreak in Minnesota resulting in death

Among unimmunized children

1 in 20 infected with Hib dies, may causepermanent brain damage in survivors

Administer at 2,4 and 6 months, boost at 12-

15 months


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Pertussis vaccine


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Now recommended for new mothers Mothers are often the source of infection of

newborns (50%)

Newborns at highest risk of disease

Obstetrics & Gynecology: February 2009 -

Volume 113 - Issue 2, Part 1 - pp 399-401


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Gardasil


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Recommended for girls 12-13 Prior to sexual activity

Or up to 26 years

3 doses in 6 months Effectively prevents HPV 6, 11, 16, and 18

Preg B

Do not administer during fever or illness Blood clots (?) and paralysis


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Immunomodulators Handout

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Transcript of Immunomodulators Handout