Immunomodulators Handout

Immunomodulators
Immunosuppressants
Immunostimulants
Vaccines
Lecture objectives
Recognize medications used to stimulate the
immune system
Recognize medications used to inhibit the
immune 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, side
effects associated with each vaccine

Southwest College of Naturopathic
Medicine
2
IMMUNOSUPPRESSION
Organ transplantation
Autoimmune disease
Medicine
3
Organ transplantation
ABO HLA matching
Multi drug therapy
Synergistic effects
Lowered toxicity
Lower dose maintenance
Evaluate for
Rejection
Toxicity
Infections
Medicine
4
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

Medicine
5
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

Medicine
6
Immunosuppressive medications
Glucocorticoids
Calcineurin inhibitors
Antiproliferative agents
Antimetabolic agents
Antibodies
Medicine
7
Problems with therapy
Life-long use
Non-specific suppression of immune system
High risk of infection
High risk of cancer
Medicine
8
Novel transplantation without
immunosuppression
Would involve co-transplanting donor stem
cells with the transplanted organ

Some liver transplants may contain
hematopoetic stem cells.

Medicine
9
IMMUNOSUPPRESSANT
MEDICATIONS
Glucocorticoids
Calcinuerin inhibitors
Cyclosporin
Tacrolimus
And other agents
Medicine
10
Corticosteroids
Examples of corticoids
Hydrocortisone
Triamcinolone
Dexamethasone
Prednisolone
Cortisone
Aldosterone
Betamethasone
Methylprednisone

Medicine
12
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
.

Medicine
13
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 and
monocytes

Medicine
14
Side effects of glucocorticoids
Growth retardation
Bone necrosis
Infection
Poor wound healing
Cataracts, glaucoma
Ulcers
Hyperglycemia
Hypertension
Dependency
Medicine
15
Toxicity of glucocorticoids
Withdrawal of therapy
Fluid and electrolyte abnormalities
Hypertension, hyperglycemia
Infections, osteoporosis, cataracts
Growth arrest
Fat redistribution
Medicine
16
Glucocorticoid Inhibitors
Mitotane, metyrapone, aminoglutethimide,
ketoconazole
Used in cancer therapies, cushings,..
Mifepristone
Medicine
17
Corticosteroids
Cortisone and prednisone must be converted to
active form by the liver
Less effective in liver disease
Medicine
18
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

Medicine
19
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

Medicine
20
Alternate day therapy
Stabilize on once daily
Then step down to alternate day
Use short or intermediate acting steroid for alternate day
dosing
Cortisone
Hydrocortisone
Prednisone
Prednisolone
Methylprednisolone
Triamcinolone

(Long acting drugs include dexamethasone and betamethasone)
Medicine
21
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
Medicine
22
Example
Minimum daily dose 30 mg prednisone
30 x 2.5 = 75
Take 75 on one day, then 30 the next
Then taper the 30 every week until discontinued
Then take 75 every other day
After stabilization, may taper 75 by 2.5/week until
lowest possible dose controls symptoms
Medicine
23
Discontinuation of therapy
Variable tapers suggested
Monitor closely for flare of disease during
taper
Any stresses may require additional dose
Medicine
24
Discontinuation of therapy
Every other day dose may be decreased by 5 mg at 1-
2 week intervals until 5 mg every other day is
reached
Then convert to hydrocortisone 20 mg/day for 2-4
weeks
Weekly reduction of hydrocortisone by 2.5 mg/week
until 10 mg/day
Then withhold a dose a take a morning cortisol level
If normal, discontinue hydrocortisone
Medicine
25
Recognize Withdrawal symptoms
Nausea, vomiting, anorexia
Headache, joint pain, fever
Lethargy, myalgia
Hypotension
Weight loss
Medicine
26
Prednisone
Taper off slowly
Interactions due to being a CYP 3A3/4
substrate
Inducers like phenytoin, rifampin decrease the
effectiveness of prednisone
Medicine
27
OTHER IMMUNOSUPPRESANTS
Medicine
28
Calcineurin inhibitors
Cyclosporine and tacrolimus
Block second messenger activity
Block induction of cytokine genes
Including IL2
Block T cell growth and differentiation
Medicine
29
Cyclosporine
Beauveria nivea fungus
Highly lipophilic
Iv or oral
Used to prevent transplant rejection
Can be used in autoimmune disease
Medicine
30
Cyclosporine
Generics not always comparable to trade
CYP 3A4 metabolism
Adjust dose in liver dysfunction
Excreted in feces
Milk

Medicine
31
Dosing cyclosporine
Usually with glucocorticoids and
antimetabolites
With sirolimus
Dosage depends on individual
Monitor
Rejection- increase dose
Toxicity- decrease dose
Medicine
32
Rheumatoid arthritis
Cyclosporine
With methotrexate and corticoids
Medicine
33
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
Medicine
34
Interactions of cyclosporine
Numerous
Inhibitors and inducers of 3A4 alter cyclosporine
concentration
Calcium channel blockers, ketoconazole,
erythromycin, methylprednisolone, protease
inhibitors, grapefruit and its juice
Nafcillin and rifampin, anticonvulsants (phenytoin)
Must closely monitor cyclosporine concentrations
Medicine
35
Cyclosporine
Increase plasma levels of
Digoxin, methotrexate, simvistatin, atorvastatin,
Requires close monitoring of these meds
Medicine
36
Cyclosporine
DO NOT substitute
Oral Sandimmune for
Neoral, Gengraf or modified cyclosporine oral
Sandimmune is less bioavailable
Neoral=Gengraf=modified oral Cyclosporine

Medicine
37
Novel uses of cyclosporine
Immunosuppression in early stages of type 1
diabetes
May delay insulin requirement in some
patients
Medicine
38
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
Medicine
39
Therapeutic uses
Prophylaxis of organ transplant
Rescue of acute rejection
Medicine
40
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
Medicine
41
Interactions
Monitor for toxicity
Renal function and blood levels
Additive toxicity with cyclosporine
Many possible interactions through 3A4
Separate antacids by 2 hours
Medicine
42
Anti-proliferative agents
Sirolimus (rapamycin, Rapamune)
Streptomyces hygroscopicus
Inhibitor of T cell activation and proliferation
Different site from cyclosporine and
tacrolimus
Medicine
43
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 carinii and cytomegalovirus

Medicine
44
Toxicity
More lymphocoele with sirolimus
Renal toxicity with cyclosporine
Anemia, leukopenia, thrombocytopenia
Hypo or hyperkalemia
Fever and GI distress
Cancer risk, infections
Medicine
45
Interactions
Numerous through CYP 3A4
Through P glycoprotein binding in serum
Cyclosporine and sirolimus interact
Separate administration by 24 hours
Monitor blood levels closely
Medicine
46
ANTI-METABOLIC AGENTS
Azathioprine
Mycophenolate mofetil
Methotrexate
Cyclophosphamide.Cytoxan
Chlorambucil/Leukeran
Leflunomide/Arava
Medicine
47
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 give
leukovorin rescue

Medicine
48
Methotrexate
Interactions
Increased toxicity by addition of
Cyclosporine, sulfonamides, high dose penicillins,
ethanol, salicylates
Methotrexate may increase cyclosporine
plasma levels and toxicity
Medicine
49
Treatment of methotrexate OD
Glucarpidase /VORAXAZE
Carboxypeptidase

Medicine
50
Azathioprine/Imuran
Purine antimetabolite
Glutathione needed to convert to 6
mercaptopurine
Inhibitor purine synthesis
Inhibits cell proliferation
Taken orally
Medicine
51
Therapeutic use of azathioprine
Kidney transplant
Prevention of rejection
Severe rheumatoid arthritis
Medicine
52
Toxicity
Bone marrow suppression
Infections
Hepatotoxic
Alopecia
GI toxic
Pancreatitis
Cancers
Medicine
53
Interactions
Allopurinol
Reduce dose of azathioprine
Care with ACE inhibitors
Medicine
54
Mycophenolate mofetil/Cellcept
Inhibitor of guanine synthesis
Decreases proliferation of T and B cells

Medicine
55
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
Medicine
56
Mycophenolate
Interactions
Antacids with aluminum or magnesium
Acyclovir, ganciclovir
Medicine
57
ANTIBODIES
Antithymocyte globulin
Muromonab CD3
Humanized anti CD3
Anti IL 2 receptor antiobies
Infliximab/Remicade
Etenercept/Enbrel
Medicine
58
Antibodies
Anti lymphocytes
Anti cell surface antigen
Poly and monoclonal
Control of polyclonal quality difficult
Medicine
59
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
Medicine
60
Toxicity
Immune reponse
Fever and chills
Hypotension
Can take with glucocorticoids to reduce effects
Serum sickness and glomerulonephritis
Rare anaphylaxis
Infection and cancer
Medicine
61
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
Medicine
62
Toxicity
Cytokine release syndrome
After 30 minutes
High fever, chills/rigor
Headache, tremor, nausea, vomiting,diarrhea
Abdominal pain, malaise
Muscle and joint aches, weakness
Severe pulmonary edema, cardiovascular collapse
Caused by release of TNF a
Prevented by glucocorticoids
Medicine
63
New generation CD3 ab
Genetically altered
Humanize to reduce reactivity to constant
regions
Less toxicity
Medicine
64
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
Medicine
65
Infliximab/remicade
Chimeric and TNF a with human constant
region
Used in inflammatory disorders
Crohns, arthritis
Causes inflammatory reactions
Fever, hypotension, infections, lupus
Medicine
66
Etanercept/Enbrel
Fusion protein TNFa receptor to Fc human
IgG1
Binds TNF a and inhibits receptor binding
Used in rheumatoid arthritis
Can cause inflammatory response
Medicine
67
Alefacept
AMEVIVE
Immunosuppressant
Dimeric fusion protein extracellular CD2 receptor of
human leukocyte antigen 3 linked to Fc region of
human IgG1
Used in psoriasis
Adverse reaction
Lymphopenia
Malignancies
Serious Infections requiring hospitalization
Hypersensitivity Reactions

Medicine
68
TREATMENT WITH IMMUNE
SUPPRESSANTS
Medicine
69
Typical treatment
Primary
Methylprednisomone
Cyclosporine
Tacrolimus
Antithymocyte globulin
Prophylaxis of infectious diseases

Medicine
70
Infectious complications
Herpes zoster most frequent
30-50%
Fungal 50%
Bacterial 50%
CMV 50%

Prophylaxis indicated
Medicine
71
FUTURE DIRECTIONS IN ORGAN
TRANSPLANTATION
Medicine
72
Co-transplant bone marrow
HLA-mismatched renal transplantation
Plus bone marrow transplantation
Successfully wean some patients off all
immunosuppressants

NEJM 2008, 358:407.
Medicine
73
Immunostimulation
Immunostimulation
Levamisole/Ergamisol
Thalidomide
Bacillus Calmett-Guerin (BCG)/Therasys
Interferons (a,b and g)
Interleukin 2/Proleukin
Medicine
75

Medicine
76
Levamisole/Ergamisol
Increases function of B, T cells and monocytes
and macrophages
Adjuvant with fluorouracil in colon cancer
Medicine
77
Thalidomide
Restricted distibution
Erythema nodosum leprosum
Decreases TNF a in leprosy
Increase TNF a in HIV
May be useful in rheumatoid arthritis
Medicine
78
LENALIDOMIDE/Revlimid
Thalidomide derivative
BBW
Pregnancy
Blood clot
Indications
Multiple myeloma
Myelodysplactic disorders

Medicine
79
LENALIDOMIDE/Revlimid
Side effects
Neutropenia, anemia
Poss. Fatal tumor lysis syndrome
Interactions
Dugixin, warfarin, other clot or platelet inhibitors
Contraindications
Pregnancy X
Medicine
80
Bacillus Calmett-Guerin
(BCG)/Therasys
Attenuated, live culture
Mycobacterium bovis
Used in carcinoma in situ
Bladder and papillary tumors
Mechanism unclear
Medicine
81
Interferons (a,b and g)
Anti-viral
Immunostimulant

Medicine
82
Interferon a2b
a2b genetically engineered E.coli
Tumors
Malignant melanoma, hairy cell leukemia,
Kaposis
Infectious disease, hepatitis B and C

Medicine
83
Interferon gamma 1b/Actimmune
Activates phagocytes
Reduces frequency and severity of chronic
granulomatous infections
Medicine
84
Interferon b 1a/Avonex, Betaseron
Antiviral
Relapsing and relapsing-remitting multiple
sclerosis
Medicine
85
Interferon side effects
Fever, headache, rash,
Flu like symptoms
a can cause cardiovascular problems
Hypotension, arrhythmias, cardiomyopathy, MI
Medicine
86
Interleukin 2/Proleukin
Enhances lymphocyte proliferation
Increases cytotoxicity and killer cell activity
Used in metastatic renal cell carcinoma
Melanoma

Can cause severe cardiovascular toxicity
Medicine
87
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
Medicine
88
Vaccination
Lecture objectives
To gain an understanding of current vaccination
practices
Describe basis of vaccination as public health care
policy
Differentiate between live attenuated and killed
vaccines, and indications for both
List the most common vaccinations and
recommendations regarding their use
Describe emerging diseases and discuss options
for protecting the populations at risk
Medicine
90
Science behind vaccination
On first exposure to a
foreign antigen
2 week latency period
before antibody
production
Memory B and T cells form
Become quiescent
On subsequent exposure
Rapid increase in antibody
production
Either complete protection
from infection or an
attenuated infection

Medicine
91
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
Medicine
92
Types of vaccines
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

Medicine
93
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
Medicine
94
Killed (inactive) vaccines
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
Medicine
95
Killed (inactive) vaccines
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.

Medicine
96
Adjuvants
Certain substances, when administered simultaneously with a specific antigen, will
enhance the immune response to that antigen. Such compounds are routinely
included 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 adjuvant is an emulsion of Mycobacteria, oil and water
Too toxic for man
Induces a good cell mediated immune response.
Incomplete Freund's adjuvant as above, but without Mycobacteria.
Muramyl di-peptide
Derived from Mycobacterial cell wall.
Cytokines
IL-2, IL-12 and Interferon-gamma.

Medicine
97
PASSIVE IMMUNIZATION
Rhogam
Medicine
98
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
ACTIVE IMMUNIZATIONS
Medicine
100
SMALL POX
Medicine
101
Smallpox
Numerous pustules
containing infectious
virus
Fatality rate Variola
major more than one
quarter of infected
patients
Variola minor has a
much lower fatality
rate (up to 5%).
Medicine
102
SMALLPOX VACCINE: A Tame Virus Runs Amok
Kaiser
Science 8 June 2007: 1418-1419
DOI: 10.1126/science.316.5830.1418
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
Medicine
103
Small pox vaccine
Multiple needle skin
prick
Sore forms, then
heals, leaving scar
Take care of the site of
injection
May cause rash, fever,
sore arm and head
and body aches

Medicine
104
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
Medicine
105
MMR
Medicine
106
Measles
Respiratory infection
with high fever
Skin rash
Medicine
107

Measles vaccine
Vaccine first introduced in 1960s
Live attenuated virus grown in chick embryo
fibroblasts
Periodic outbreaks in previously vaccinated
college students.
Administered at 12 months in MMR
Booster at 11-12 years.
Medicine
108
Mumps
febrile illness
swollen salivary glands
Lasts about a week
spread by the respiratory route
21 days incubation period.
Aseptic meningitis common complication
Mumps meningoencephalitis is rarer but a more serious.
Orchitis can occur, more often after puberty, unilateral or
bilateral, but is rarely followed by infertility. Other glandular
tissue is very occasionally involved pancreatitis, oophoritis or
thyroiditis.
Diagnosis can be confirmed by positive IgM antibodies. In
cases of meningitis the virus is readily isolated from cerebro-
spinal fluid.
Medicine
109
Mumps vaccine

Live attenuated virus developed in the
1960's.
administered with measles and rubella at 12-
15 months in the MMR vaccine.

Medicine
110
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 between
about the 13th and the 17th week
of pregnancy may result in
deafness alone, but infection
beyond the 17th week is no longer
a hazard.
Medicine
111

Rubella vaccine

Live attenuated virus.
Administered at 12-15 months in MMR
Booster at 11-14 years

Medicine
112
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

Medicine
113
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

Medicine
114
POLIO
Medicine
115
Polio
All polio in US is currently
vaccine related (up to 16
cases per year)
Virus lives in gut, spreads
through oral-fecal route,
particularly in swimming
pools.
Virus infects neurons,
causing paralysis of
different muscles
Post-polio syndrome

Medicine
116
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 are
immunosuppressed.
Adminstered at ages 2 months, 4 months, 6-18 months, and 4-6 years

Medicine
117
Polio vaccines
Contraindications
-Severe allergic reaction to previous dose or
vaccine component
Precautions
-Pregnancy
-Moderate or severe acute illness with or
without fever
Medicine
118
HEPATITIS
Medicine
119
Hepatitis B
Clinical Features
Incubation period 2 - 5 months
Pathogenesis
parenterally transmitted. Blood highly infections
Complications
1) Persistant infection:-
5% become persistantly infected.
Chronic infection may take one of two forms:
Chronic persistent Hepatitis - the virus persists, minimal liver damage
Chronic Active Hepatitis - cirrhosis or liver failure.
2) Patients who become persistently infected are at risk of developing
hepatocellular carcinoma (HCC)..
3) Fulminant Hepatitis
1% of infections
Hep B globulin available for needlestick injuries
Medicine
120
Hepatitis B
Two vaccines are in
current use:
serum derived vaccine
recombinant vaccine.
The serum derived
vaccine is prepared from
hepatitis B surface
protein, purified from the
serum of hepatitis B
carriers.
Three doses are given; at
6, 10, and 14 weeks of
age.
Booster at 10 years or so

Medicine
121

Hep B vaccine
Contraindications
vaccine component

Precautions
-Infant weighing < 2,000 grams
without fever
Medicine
122
Hepatitis A - "Infectious Hepatitis"
Clinical Features
Incubation period 3-5 weeks (mean 28 days)
Milder disease than Hepatitis B; asymptomatic infections are very common, especially in
children.
Adults, especially pregnant women, may develop more severe disease.
Although convalescence may be prolonged, there is no 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 of
symptoms.
Transmission - Enteric
Large 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
Diagnosis
Virus cannot be cultured in vitro from clinical material, and diagnosis is made on the
presence of HAV-specific IgM in the patient's blood.
Medicine
123
Passive immunity
Normal immunoglobulin given to:
Travelers to third world countries
Household contacts of acute cases

Medicine
124
Hepatitis A vaccine

formalin-inactivated, cell culture-derived
virus.
Two doses, administered one month apart,
The vaccine is recommended for travellers to
third world countries.

Medicine
125
Hep A side effects
soreness at the injection site (56%), headache
(14%), and malaise (7), feeding problems (8%),
headache (4%), and injection-site induration
(4%).
Medicine
126
Hep A vaccine
Contraindications
vaccine component

Precautions
-Pregnancy
without fever
Medicine
127
DTP
Diphtheria
Pertussis
Tetanus
Medicine
128
DTaP
Contraindications
-Severe allergic reaction after a previous dose or to a vaccine component
-Encephalopathy (e.g., coma, decreased level of consciousness; prolonged
seizures) within 7 days of administration of previous dose of DTP or DTaP
-Progressive neurologic disorder, including infantile spasms, uncontrolled
epilepsy, progressive encephalopathy; defer DTaP until neurologic status
clarified and stabilized.

Precautions
-Fever of >40.5 C <48 hours after vaccination with a previous dose of DTP
or DTaP
-Collapse or shock-like state (i.e., hypotonic hyporesponsive episode) <48
hours after receiving a previous dose of DTP or DTaP
-Seizure <3 days of receiving a previous dose of DTP/DTaP^
-Persistent, inconsolable crying lasting >3 hours <48 hours after receiving
a previous dose of DTP or DTaP
-Moderate or severe acute illness with or without fever
Medicine
129
DT, Td
Contraindications
-Severe allergic reaction after a previous dose
or to a vaccine component

Precautions
-Guillain-Barr syndrome <6 weeks after
previous dose of tetanus toxoid-containing
vaccine
without fever
Medicine
130
YELLOW FEVER
Medicine
131
Yellow Fever vaccine

live attenuated vaccine
developed in 1937
administered to residents in the tropics and
travellers to endemic areas
A single dose induces protective immunity to
travellers and booster doses, every 10 years,
are recommended for residents in endemic
areas.

Medicine
132
RABIES
Medicine
133
Rabies
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.

Medicine
134
INFLUENZA
Medicine
135
Influenza

New vaccines prepared yearly
vaccines consist of partially purified envelope
proteins of inactivated current influenza A and B
strains.
Who should receive vaccine
Individuals who are at risk of developing severe, life
threatening disease if infected with influenza
Includes the elderly, immunocompromised, and patients
with cardiac disease. In these patients, protection from
disease is only partial, but the severity of infection is
reduced.

Medicine
136
Influenza vaccine
Contraindications
vaccine component, including egg protein

Precautions
without fever
Medicine
137
NOVEL H1N1 INFLUENZA
Swine flu
Medicine
138
H1N1 vaccine
Produced using the same methods as seasonal
flu
Live attenuated intranasal vaccine
Injected killed vaccine
Two shots, one month apart, for children
under 9
Medicine
139
H1N1 vaccine 2009
CDC guidelines
pregnant women,
persons who live with or provide care for infants aged
<6 months (e.g., parents, siblings, and daycare
providers),
health-care and emergency medical services
personnel,
persons aged 6 months--24 years, and
persons aged 25--64 years who have medical
conditions that put them at higher risk for influenza-
related complications

Medicine
140
CHICKEN POX
Medicine
141
Varicella zoster
This is a common
childhood infection
mild febrile illness
generalized vesicular
rash.
21 days incubation
period.
The lesions progress from
macule to papule to
vesicle to pustule to scab.

Medicine
142

Varicella zoster vaccine
A live attenuated strain of varicella zoster virus
Used to protect immune compromised
children
Required in AZ at 12 months and 2 years
Medicine
143
Varicella Zoster vaccine
Contraindications
-Severe allergic reaction to previous dose or vaccine
component
-Substantial suppression of cellular immunity
-Pregnancy

Precautions
-Recent (<11 months) receipt of antibody-containing
blood product (specific interval depends on product)
$$
-Moderate or severe acute illness with or without
fever
Medicine
144
ROTAVIRUS
Medicine
145
Rotavirus
Most common cause of severe diarrhea
(hospitalization) in infants and children in US
Most children infected before 2 years old
Most infection between November and May
2 day incubation, oral/fecal transmission
Vomiting and diarrhea last 3-8 days

Medicine
146
Rotarix, RotaTeq
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
Medicine
147
CI RotaTeq
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

Medicine
148
5-2010 update
Lots of Rotarix and RotaTeq contain PCV1
and/or PCV2 (porcine circovirus)
Not known to cause illness in people
Considered appropriate to continue to use
these vaccines until more information has
become available
Medicine
149
RECENT UPDATES
Medicine
150
Hemophilus influenzae type B
January 09
Outbreak in Minnesota resulting in death
Among unimmunized children
1 in 20 infected with Hib dies, may cause
permanent brain damage in survivors
Administer at 2,4 and 6 months, boost at 12-
15 months
Medicine
151
Pertussis vaccine
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

Medicine
152
Gardasil
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
Medicine
153

Medicine
154

Immunomodulators Handout

Hochgeladen von

Dokumentinformationen

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Immunomodulators Handout

Hochgeladen von

Copyright:

Verfügbare Formate

Immunomodulators

Das könnte Ihnen auch gefallen