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70 Cards in this Set

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What are the Principles of Vaccination
Immunity - Self vs. non-self - Protection from infectious disease
Active Immunity - Protection produced by a person's own immune system - Usually permanent
Passive Immunity - Protection transferred from another person or animal as antibody
Passive Immunity
Transfer of antibody from an exogenous source
Transplacental most important source in infancy 3rd trimester of preg)
Temporary protection
Almost all blood or blood products
Homologous pooled human antibody (immune globulin)
Homologous human hyperimmune globulin
Heterologous hyperimmune serum (antitoxin)
Classification of Vaccines
Live attenuated
Bacterial
Viral

Inactivated
Subunit Vaccines
Toxoid Vaccines
Conjugate Vaccines
DNA Vaccines
Recombinant Vector Vaccines
Inactivated Vaccines - what kinds are made and what are the pros and cons?
virus
bacteria
protein-based: subunit, toxoid
polysaccharide-based: pure, conjugate
Scientists produce inactivated vaccines by killing the disease-causing microbe with chemicals, heat, or radiation. Such vaccines are more stable and safer than live vaccines: The dead microbes can’t mutate back to their disease-causing state. Inactivated vaccines usually don’t require refrigeration, and they can be easily stored and transported in a freeze-dried form, which makes them accessible to people in developing countries.

Most inactivated vaccines, however, stimulate a weaker immune system response than do live vaccines. So it would likely take several additional doses, or booster shots, to maintain a person’s immunity. This could be a drawback in areas where people don’t have regular access to health care and can’t get booster shots on time.
Live, Attenuated Vaccines what kinds are made and what are the pros and cons?
Attenuated (weakened) form of the "wild" virus or bacteria
Must replicate to be effective
Immune response similar to natural infection
Usually effective with one dose
Severe reactions possible
Interference from circulating antibody
Unstable

Live, attenuated vaccines contain a version of the living microbe that has been weakened in the lab so it can’t cause disease. Because a live, attenuated vaccine is the closest thing to a natural infection, these vaccines are good “teachers” of the immune system: They elicit strong cellular and antibody responses and often confer lifelong immunity with only one or two doses.

Despite the advantages of live, attenuated vaccines, there are some downsides. It is the nature of living things to change, or mutate, and the organisms used in live, attenuated vaccines are no different. The remote possibility exists that an attenuated microbe in the vaccine could revert to a virulent form and cause disease. Also, not everyone can safely receive live, attenuated vaccines. For their own protection, people who have damaged or weakened immune systems— because they’ve undergone chemotherapy or have HIV, for example—cannot be given live vaccines.

Another limitation is that live, attenuated vaccines usually need to be refrigerated to stay potent. If the vaccine needs to be shipped overseas and stored by health care workers in developing countries that lack widespread refrigeration, a live vaccine may not be the best choice.
Live Attenuated Vaccines - Which ones are viral?
Viral
measles, mumps, rubella, vaccinia, varicella, yellow fever (oral polio) (influenza) (rotavirus)
Live Attenuated Vaccines - Which ones are bacterial?
Bacterial
BCG, oral typhoid
Live Attenuated Vaccines - What makes bacterial vaccines difficult to make?
Live, attenuated vaccines are more difficult to create for bacteria. Bacteria have thousands of genes and thus are much harder to control. Scientists working on a live vaccine for a bacterium, however, might be able to use recombinant DNA technology to remove several key genes. This approach has been used to create a vaccine against the bacterium that causes cholera, Vibrio cholerae, although the live cholera vaccine has not been licensed in the United States.
Live Attenuated Vaccines - What makes viral vaccines easier to make?
Live, attenuated vaccines are relatively easy to create for certain viruses. Vaccines against measles, mumps, and chickenpox, for example, are made by this method. Viruses are simple microbes containing a small number of genes, and scientists can therefore more readily control their characteristics. Viruses often are attenuated through a method of growing generations of them in cells in which they do not reproduce very well. This hostile environment takes the fight out of viruses: As they evolve to adapt to the new environment, they become weaker with respect to their natural host, human beings.
Inactivated Vaccines - pros and cons
Cannot replicate
Minimal interference from circulating antibody
Generally require 3-5 doses
Antibody titer falls over time
Inactivated Vaccines - which ones are viral
Viral
influenza, polio,
rabies, hepatitis A
Inactivated Vaccines - Inactivated Vaccines - which ones are bacterial?
Bacterial
pertussis, typhoid, cholera, plague
Inactivated Vaccines - Inactivated Vaccines - which ones are subunit?
Subunit
hepatitis B, influenza, typhoid Vi, Lyme
Inactivated Vaccines - Inactivated Vaccines - which ones are toxoid?
Toxoid
diphtheria, tetanus
Inactivated Vaccines - what does NIAID say?
Inactivated Vaccines

Scientists produce inactivated vaccines by killing the disease-causing microbe with chemicals, heat, or radiation. Such vaccines are more stable and safer than live vaccines: The dead microbes can’t mutate back to their disease-causing state. Inactivated vaccines usually don’t require refrigeration, and they can be easily stored and transported in a freeze-dried form, which makes them accessible to people in developing countries.

Most inactivated vaccines, however, stimulate a weaker immune system response than do live vaccines. So it would likely take several additional doses, or booster shots, to maintain a person’s immunity. This could be a drawback in areas where people don’t have regular access to health care and can’t get booster shots on time.
Subunit Vaccines - what does NIAID say?
Subunit Vaccines

Instead of the entire microbe, subunit vaccines include only the antigens that best stimulate the immune system. In some cases, these vaccines use epitopes—the very specific parts of the antigen that antibodies or T cells recognize and bind to. Because subunit vaccines contain only the essential antigens and not all the other molecules that make up the microbe, the chances of adverse reactions to the vaccine are lower.

Subunit vaccines can contain anywhere from 1 to 20 or more antigens. Of course, identifying which antigens best stimulate the immune system is a tricky, time-consuming process. Once scientists do that, however, they can make subunit vaccines in one of two ways:
•They can grow the microbe in the laboratory and then use chemicals to break it apart and gather the important antigens.
•They can manufacture the antigen molecules from the microbe using recombinant DNA technology. Vaccines produced this way are called “recombinant subunit vaccines.”

A recombinant subunit vaccine has been made for the hepatitis B virus. Scientists inserted hepatitis B genes that code for important antigens into common baker’s yeast. The yeast then produced the antigens, which the scientists collected and purified for use in the vaccine. Research is continuing on a recombinant subunit vaccine against hepatitis C virus
Toxoid Vaccines - what does NIAID say?
Toxoid Vaccines

For bacteria that secrete toxins, or harmful chemicals, a toxoid vaccine might be the answer. These vaccines are used when a bacterial toxin is the main cause of illness. Scientists have found that they can inactivate toxins by treating them with formalin, a solution of formaldehyde and sterilized water. Such “detoxified” toxins, called toxoids, are safe for use in vaccines.

When the immune system receives a vaccine containing a harmless toxoid, it learns how to fight off the natural toxin. The immune system produces antibodies that lock onto and block the toxin. Vaccines against diphtheria and tetanus are examples of toxoid vaccines.
Conjugate Vaccines
- what does NIAID say?
Conjugate Vaccines

If a bacterium possesses an outer coating of sugar molecules called polysaccharides, as many harmful bacteria do, researchers may try making a conjugate vaccine for it. Polysaccharide coatings disguise a bacterium’s antigens so that the immature immune systems of infants and younger children can’t recognize or respond to them. Conjugate vaccines, a special type of subunit vaccine, get around this problem.

When making a conjugate vaccine, scientists link antigens or toxoids from a microbe that an infant’s immune system can recognize to the polysaccharides. The linkage helps the immature immune system react to polysaccharide coatings and defend against the disease-causing bacterium.

The vaccine that protects against Haemophilus influenzae type B (Hib) is a conjugate vaccine.
Recombinant Vector Vaccines - what does NIAID say?
Recombinant Vector Vaccines

Recombinant vector vaccines are experimental vaccines similar to DNA vaccines, but they use an attenuated virus or bacterium to introduce microbial DNA to cells of the body. “Vector” refers to the virus or bacterium used as the carrier.

In nature, viruses latch on to cells and inject their genetic material into them. In the lab, scientists have taken advantage of this process. They have figured out how to take the roomy genomes of certain harmless or attenuated viruses and insert portions of the genetic material from other microbes into them. The carrier viruses then ferry that microbial DNA to cells. Recombinant vector vaccines closely mimic a natural infection and therefore do a good job of stimulating the immune system.

Attenuated bacteria also can be used as vectors. In this case, the inserted genetic material causes the bacteria to display the antigens of other microbes on its surface. In effect, the harmless bacterium mimics a harmful microbe, provoking an immune response.

Researchers are working on both bacterial and viral-based recombinant vector vaccines for HIV, rabies, and measles.
what family does measles come from?
Paramyxovirus, related to canine distemper
MEASLES Epi
Epidemiology:
1. Requires several thousand people to propagate--URBAN
 
2. Independent of vector, epidemiology depends on human factors
Endemic year-round in tropical areas with outbreaks every 2-5 years
Outbreaks may be explosive in all ages in isolated areas
Measles: Risk Factors for severe disease
Vitamin A deficiency--increased risk disease, blindness

Malnutrition--Cause vs. effect?

Low vaccination coverage

Age--maternal antibodies last 8-9 mo. in tropics 35% cases between 6-12 mo.; 50% by 24 mo.

Low maternal antibody levels in developing countries--?diarrhea, ?less disease

Family size/group exposure
 
Case fatality rate 5-10% in tropical Africa, vs.
0.01% to 0.1% in U.S.
Measles: Clinical Features
Incubation period
10-12 days
Measles: Clinical Features
Prodrome
Prodrome--3-4 days of fever 38.5oC, coryza, cough, conjunctivitis, Koplik spots 1-2 d prior to rash
Pharynx and tongue tip red, occ. Exudate tracheobronchitis (croup) VERY common COMMUNICABLE from start of prodrome to 2 d. into rash.
Malnutrition results in longer communicability
Measles: Clinical Features
Post Prodrome
Rash--starting at hairline, spreads inferiorly
"measly appearance" (red eyes, swollen nasal bridge, copious thin nasal secretions)

Onset of rash correlates with initial IgG, IgM (Hemagglutination Inhibition, Plaque Nuetralization)

Discrete macules coalesce to form irregular red maculopapular rash
Measles: Complications
1) Hemorrhagic Measles--bleeding into rash with purpura
May be associated with GI or CNS bleeding
Vasculitis and thrombocytopenia
 
2. Bacterial superinfection--otitis, pneumonia, pyoderma

3. Hecht's giant cell pneumonia--frequently without rash -- Often fatal, usually adults
 
4.Diarrheal diseases--contributes to death in severe disease

Higher rate of other diarrheal diseases in next year associated with cellular immunosuppression

May be associated with GI or CNS bleeding
Vasculitis and thrombocytopenia

5) Atypical Measles In recipients of killed measles vaccine

6) Atypical Measles After receiving injectable immune globulin

7) Measles Encephalitis

8) Subacute sclerosing panencephalitis (SSPE)
 
what is toxic measles
extreme erythema
hemorrhagic lesions
Describe - Atypical Measles In recipients of killed measles vaccine
In recipients of killed measles vaccine, who develop hypersensitivity rather than protective immunity
Hemorrhagic rash, pneumonia, high fever
Describe - Atypical Measles After receiving injectable immune globulin
After receiving injectable immune globulin, symptoms are blunted, rash is not typical
Measles Encephalitis - how many get it?
What is the morbidity mortality rates?
0.5 to 1% of cases, usually in most severe cases, older patients

10-30% mortality, 40% survivors with sequelae
 
Measles Encephalitis when does it occur?
What are symptoms?
Occurs 3-5 days after onset rash
 
Renewed fever, vomiting, drowsiness, seizures, coma
Measles Encephalitis - what are csf finds?
CSF findings--lymphocytosis, normal or high protein/glucose
Subacute sclerosing panencephalitis (SSPE) when do you get it?
What are the Si/Sx?
Occurs years after infection

Progressive mental deterioration, myoclonic jerks
 
Abnormal EEG with periodic high voltage complexes
Measles: Diagnosis
1. Clinical presentation—
Prodrome
Koplik spots appear early
Character of rash
WBC count as low as 1,500 with relative lymphocytosis
CXR shows patchy pneumonic/perihilar pattern
Measles: Differential Diagnosis:
Rubella--less catarrhal (Inflammation of mucous membranes, especially of the nose and throat)
Scarlatina--less catarrhal, more papular
Typhoid
Serum sickness
Allergic rash (esp. ampicillin)
Measles: Diagnosis
Laboratory--Serological assays
 
Plaque Neutralization--gold standard, neutralizing antibody - Most expensive and time-consuming
(requires live virus, hood)
 
ELISA--easy, cheap, no reader, sensitive, polyclonal

Hemagglutination Inhibition--less reliable, expensive
Measles: Management
Supportive measures:
Fever reduction
Airway management (clear secretions)
Cleansing conjunctivae
Maintain fluids
HIGH PROTEIN/HIGH CALORIE DIET
Oral vitamin A--250,000 IU po qd x 2
Measles: Control Measures
1. Quarantine--Generally not useful, stopgap till vaccine available

2. Measles vaccine—Considerations for use:
Regional variation in maternal antibody
Age of vaccination (6 months vs. 9 months)
Little vaccine virus spread
Effect of vaccine strain and dose
Measles Immune Globulin or Immune Serum Globulin
Measles: Control Measures
Vaccines currently in use:
Vaccines currently in use:
Schwartz
Moraten
Edmonston-Zagreb
At appropriate age, vaccine induces antibody in 95% (but outbreaks occur with 99% coverage)

DO NOT WITHHOLD VACCINE FOR MILD/MODERATE FEVER, COMMON COLD, OR MALNUTRITION
Measles: Control Measures
Measles Immune Globulin or Immune Serum Globulin—
Measles Immune Globulin or Immune Serum Globulin—May prevent disease if given within 6 days of exposure;

Dose MIG or ISG: 0.25 cc/kg. body weight I.M. (maximum 15 cc)
types of measles vaccines
Schwartz - standard-titer (ST)

high-titer (HT) Edmonston-Zagreb (EZ) measles vaccines.
Issues between Schwartz and Edmonston-Zagreb (EZ) measles vaccines.
No difference in vaccine efficacy was found between HT and ST measles vaccines.

The mortality rate for EZ-HT vaccine recipients was
not higher than that for measles-unvaccinated children. In the study of the routine use of
EZ-HT measles vaccine, the children who received
EZ-HT had significantly lower mortality rates between
9 and 24 months of age than did those who did not
receive the measles vaccination.

EZ more immungenic at 6 and 9 months than Schartz

increased dose of EZ worked better than increased dose of Schartz

The most notable feature of the HT measles vaccine problem undoubtedly was the nearly two-fold increased
incidence of mortality observed among girls receiving the live HT measles vaccine compared with the ST measles vaccine.
Measles vs. Tetnus:
Can the vaccine produce disease?
Measles is a live attenuated vaccine - yes - The remote possibility exists that an attenuated microbe in the vaccine could revert to a virulent form and cause disease.
are weak versions of the disease viruses, they may cause a very mild case of the disease they were designed to prevent; however, it is usually much milder than the natural disease and is referred to as an adverse reaction to the vaccine.

Tetnus - n0 - The dead microbes can’t mutate back to their disease-causing state.
Measles vs. Tetnus:
Is it contraindicated in HIV persons?
Meales - yes - not everyone can safely receive live, attenuated vaccines. For their own protection, people who have damaged or weakened immune systems— because they’ve undergone chemotherapy or have HIV, for example—cannot be given live vaccines

Tetnus - not contraindicated
Measles vs. Tetnus: does it provide herd immunity?
Measles - yes -

Tetnus - no -
Herd immunity only applies to diseases that are contagious. It does not apply to diseases such as tetanus (which is infectious, but is not contagious), where the vaccine protects only the vaccinated person from disease.[8] Herd immunity should not be confused with contact immunity, a related concept wherein a vaccinated individual can 'pass on' the vaccine to another individual through contact.
Measles vs. Tetnus:
Do passive Abs interfere with it?
Measles - Yes - maternal Ab is transferred transplacetnally and this inhibits vaccine efficacy up to the age of 6 months.

Tetnus - no - maternal and neonatal tetnus (MNT) can be prevented through immunization of the mother in pregnancy. UNICEF goal to eliminate MNT by 2005. main strategies: promotion of clean dellivery practices, immunize women with tetanus toxoid, surveillance.
Most developing countries have implemented this.
Developing countries are encouraged to do so, in addition to routing imms, all women of child bearing age living in high risk areas are targeted for immunization with three doses of TT.
What causes tetnus?
Clostridium tetani, anaerobic, gram-positive rod
what is herd immunity?
Herd immunity (or community immunity) describes a form of immunity that occurs when the vaccination of a significant portion of a population (or herd) provides a measure of protection for individuals who have not developed immunity.
Herd immunity theory proposes that, in contagious diseases that are transmitted from individual to individual, chains of infection are likely to be disrupted when large numbers of a population are immune or less susceptible to the disease. The greater the proportion of individuals who are resistant, the smaller the probability that a susceptible individual will come into contact with an infectious individual.
Major clostridial diseases:
Major clostridial diseases:

Tetanus--C. tetani
Botulism--C. botulinum
Gas gangrene--C. perfringins
Intestinal--C. difficile, C. perfringins
What is the other name for tetnus?
lockjaw
TETANUS: Epidemiology
1. Present on many surfaces (dirt, manure, animal hair, plaster)
More common in rural/agricultural areas
2. No person-to-person spread
3. Infection due to introduction spores into tissues (surgery, burns, tatoo, abortions, ear piercing,skin infections, insect bites)
Neonatal--through umbilical stump
TETANUS: Epidemiology fatality rate
High fatality rate--1 million deaths annually
 
Deaths are preventable with immunization and prophylaxis
TETANUS: Epidemiology
Risk factors
Risk factors:
Ritual practices
Neonates and Elderly
Poverty
TETANUS: Clinical Manifestations - Incubation Period-
Incubation Period--3 to 10 days
TETANUS: Clinical Manifestations - What causes clinic features?
Clinical Features due to Tetanus toxin, which blocks inhibitory nerve signal at the neuromuscular junction, resulting in muscle spasms
TETANUS: Clinical Manifestations
Clinical Manifestations--peak 1 week after onset,
Clear in 3 weeks in survivors
Generalized increased muscle tone and reflexes
Masseter rigidity (trismus)
Local paresthesias (tingling sensations)
Local spasms--risus sardonicus (creased forehead, tight lips)
Visual, auditory stimuli --> spasms
Respiratory dysfunction (cyanosis, apnea)
Swallowing dysfunction
Sympathetic overactivity--sweating,salivation, tachycardia, blood pressure swings
SENSORIUM INTACT--Conscious and alert
TETANUS: Clinical Manifestations - Newborn infection:
Newborn infection:
 
Symptoms usually after first week of life
Difficulty in sucking is first sign
Convulsions common at onset
Characteristic posturing hyperflexion/adduction of arms, clenched fists, hyperextension of legs
Painful spasms with noise, light touch
Mortality 70%
TETANUS: Clinical Manifestations - Localized tetanus:
Localized tetanus:

Rigidity, spasm localized to inoculation site
Symptoms last weeks but most recover
Cephalic tetanus--localized to cranial nerves
TETANUS: Clinical Manifestations - Complications
Complications
 
1. Omphalitis (infection of the umbilical cord stump in the neonatal newborn period )--newborn
2. CNS/meningitis--newborn
3. Pulmonary disease--aspiration pneumonia, diaphragm paralysis
4. Mouth/GI ulcers--rel. tissue hypoxia
5. Cranial nerve palsies
6. Vertebral fractures
TETANUS: Diagnosis
1. Clinical Manifestations and compatible history
Bacteriologic isolation unreliable, no acute serologic response
Mild leukocytosis, enzyme elevations with spasm
 
TETANUS: DiagnosisDifferential Diagnosis:
Differential diagnosis--
Hypocalcemia--spasms mainly in limbs
Poisonings (carbon monoxide, phenothiazines, narcotic withdrawal)
Rabies--progresses more rapidly, no trismus, rigidity uncommon
TETANUS: DiagnosisDifferential Diagnosis of Trismus:
Differential Diagnosis of Trismus:

Mumps,
Mandibular fracture,
Dental abscess,
Temporomandibular arthralgia from serum sickness

In non-tetanic trismus, pressure allows mouth to open
TETANUS: Treatment
1) Nursing Care
2) Antitoxin:
3. Antibiotics—
Penicillin G 100,000 U/kg/day divided qid for 10-14 days
Tetracycline

4. Local wound care/drainage
 
5. Sedatives/muscle relaxants-
TETANUS: Treatment - Antitoxin:
) Antitoxin:
Effects only circulating toxin
Tetanus Immune Globulin 3000-6000 units
Equine Tetanus Antitoxin (requires sensitivity testing) 50,000-100,000 units
Immune Globulin Intravenous
TETANUS: Treatment - Sedatives/muscle relaxants--spasm control vs. sedation
Sedatives/muscle relaxants--spasm control vs. sedation
For spasms--diazepam 1-5mg/kg/d continuous slow IV
diazepam can also be given po
alternative: chlorpromazine IM or IV 25 mg/kg q 6-8 hours
TETANUS: Prevention
Immunization Programs:

Tetanus toxoid vaccine given in combination with diptheria toxoid and pertussis (whooping cough) vaccine (DPT or dT)
 
Infants: 3 injections during the first year, booster at school entry and every 10 years if high risk
 
Pregnant Women: if unimmunized, vaccinate during first 7 months (immunization of pregnant women is the best method for prevention of neonatal tetanus)
tetanus prophylaxis in routine wound management - Clean, minor wounds
History of tetanus toxoid is unknown or <3 doses
Td - Yes
TIG - No

tetanus and diphtheria toxoids (Td) for adults is preferred to TT alone. TIG=tetanus immune globulin
tetanus prophylaxis in routine wound management - Clean, minor wounds
History of tetanus toxoid is >=3 doses
Td- No
TIG - No** . ** Yes, if >10 years have elapsed since last dose

tetanus and diphtheria toxoids (Td) for adults is preferred to TT alone. TIG=tetanus immune globulin
tetanus prophylaxis in routine wound management - All other wounds *
History of tetanus toxoid is unknown or <3 doses

* Such as, but not limited to, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns, or frostbite.
Td - Yes
TIG - Yes

tetanus and diphtheria toxoids (Td) for adults is preferred to TT alone. TIG=tetanus immune globulin
tetanus prophylaxis in routine wound management - All other wounds *
History of tetanus toxoid is >=3 doses

* Such as, but not limited to, wounds contaminated with dirt, feces, soil, or saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns, or frostbite.
Td - No++
TIG No
++ Yes, if >5 years have elapsed since last dose. (More frequent boosters are not needed and can accentuate side effects.)