Antiviral agents vaccines and immunotherapies - part 8 ppsx

immu-MEASLES, MUMPS, AND RUBELLA VACCINES Measles, mumps, and rubella are described in Chapter 3.Each of these viruses has its own vaccine to be described later.The vaccination for these

Vaccines and Immunotherapies 295

oral polio vaccine, and some adenovirus vaccines areexamples of attenuated live viral vaccines

Killed viral vaccines (inactivated) Whole virus

parti-cles or some component of the virus, either of which hasbeen deactivated chemically or physically These vac-cines do not cause infection but stimulate an immunereaction Usually, repeated doses are required as onedose does not confer lifelong immunity Large quanti-ties of viral antigens per dose are necessary to produce

an adequate response Influenza, Salk polio, rabies, andJapanese encephalitis vaccines are of this type

Recombinant antigens Tend to be newer versions of

earlier vaccines and furnish better protection with lessrisk and fewer side effects Specific components that elicitproduction of protective antibodies are cloned Theseexpress the gene that encodes that protein or proteincomplex The new hepatitis B vaccine is this type.The different types of vaccines that produce immuneresponses in a variety of cell types are shown in Table 4.2.Vaccine-induced immunity is a relative science Selecting thecorrect dosage(s), timing of dosages, and determining the long-term efficacy are trials facing vaccine development Normally,

func-tions B-cell functions may involve secretion of IgG antibodies

leukocyte antigen (HLA)-matched infected cells B cells, whenmediated by T-helper cells, are thought to provide long-lastingimmunity despite negative antibody test results (2)

Immune System Development

B-cells Live-attenuated virus vaccines, inactivated

virus vaccines, protein antigens, capsular polysaccharides with or without carrier CD8 + T cells Live-attenuated virus vaccines.

CD4+ T cells Live-attenuated virus vaccines, inactivated

virus vaccines, protein antigens, and capsular polysaccharides only with a protein carrier.

The development of vaccines may take decades to terize, develop genetic-splicing methods to improve safety andefficacy, and complete appropriate testing Still, even aftervaccines are developed, many persons choose for a variety ofreasons not to be vaccinated Therefore antivirals, prophylaxistherapies, vaccines, and other immunomodulators all have arole to play in disease eradication and cure.

charac-SMALLPOX AND OTHER POXVIRUSES

Smallpox

In 1796, Edward Jenner first demonstrated that inoculation ofcowpox virus into human skin could lead to protection fromsubsequent smallpox infection (3) He named the inoculation

substance vaccine, based on the Latin word, vacca, meaning cow The more effective vaccines used for smallpox vaccination

are derived from the vaccinia virus that is similar to cowpox.Several strains of the live attenuated virus vaccine wereemployed in eradication of the disease The smallpox vaccinehas been the prototype of success of a viral vaccine Prior toimmunization, smallpox infection relentlessly killed hundreds

of millions of persons and left many badly scarred and/orblind The mortality rate ranged between 20–30% The world-wide eradication of this disease in 1977 is considered thegreatest success story in medical history The recent acciden-tal introduction of monkeypox into the United States via theGambian pouched rat illustrates the need for better vaccinesand perhaps vaccines with a broader range of targets Immu-nity provided by the current smallpox vaccination reduces theeffects of monkeypox virus on humans by 85%

Vaccine production ended two decades ago and most icans under the age of 35 have not been vaccinated Smallpoxeradication occurred because every child was immunized beforeattending public school, thus reducing the exposure of infectedchildren to nonimmunized children and their families (4).Approximately 60 million vaccine doses remain worldwide andmore vaccine is bring produced (5) Immunologic status of theolder population is questionable but there are some reports of

Amer-lingering immunity (6–8) At least 119,000,000 people in theUnited States have never been immunized (9) There are someindications from recent revaccinations of older persons thatsome degree of immunity still exists, albeit variable among thepopulation The destruction of the two remaining smallpox virusreserves in Atlanta and near Moscow has been a source of ongo-ing debate Opponents of destruction contend that the virusstocks would be helpful for future research, such as smallpoxpathogenesis and the production of new antiviral agents (10,11).Fear of undisclosed reserves is also a concern Proponents arguethat the virus genome has already been cloned and sequencedand is unnecessary for research (12).

Destruction of the virus reserves will likely be halted asconcerns for bioterrorism increase Of concern since the col-lapse of the Soviet Union is that existing stocks of virus, com-bined with the technology for maintaining and activating thestocks, may have passed into non-Russian hands (13) Shouldthese undocumented virus stocks fall into the domain of ter-rorists, strategic outbreaks among the unvaccinated or under-immunized could begin an epidemic that would be difficult tocontain Smallpox is considered to be an ideal bioterroist ave-nue as it is easily transmitted, has a high mortality rate,requires specific action for public health response, and could

cause social and community disarray (14) Models based on

the assumption that 100 persons are initially infected andeach infects three more predict that quarantine could stop oreradicate such an outbreak if 50% of those with overt symp-toms were quarantined At risk would be family members(50% risk to the unvaccinated), school children, health-careworkers, etc Vaccination alone would only stop the transmis-sion within a year if the disease transmittal rate were reduced

to <0.85 persons infected per initially infected person fore, a combination vaccination-quarantine program is neces-sary (25% daily quarantine and a vaccination reduction ofsmallpox transmission by >33%) Given the scenario, approx-imately 4,200 cases would occur over the period of a year.Approximately 215,500 vaccine doses would need to be admin-istered to stop the outbreak (15) Vaccination distributionusing two distinct models predicts that mass vaccination (MV)

There-is superior over traced vaccination (TV) TV involves contacttracing with susceptible and exposed individuals beingadministered the vaccine, whereas MV occurs when everyone

is vaccinated simultaneously according to a schedule In thesemodels, MV results in both fewer deaths and more rapid reso-lution of an epidemic (16) Vaccine production remains limitedalthough numbers of available vaccine stock are increasing.Plans are to voluntarily vaccinate smallpox response teams,public health authorities and staff, and some law enforcementstaff The military were the first to be vaccinated (17)

Smallpox transmission occurs via droplets or as an sol from the respiratory tract or by fomite exposure to bed-ding or clothing An incubation period of 7–17 days (average of

aero-12 days) is followed by a fever for 2–4 days A rash ensues thatlasts for weeks as papules become vesicles, followed by pus-tules and scabs A characteristic of smallpox that separates itfrom the initial chickenpox diagnosis is that all skin eruptions

in a localized area are in the same stage at any given point intime Chickenpox lesions are more superficial than the hard,deep-seated lesions of smallpox Localized eruptions of HSV-2may mimic smallpox (18) Disease transmission may occur asthe fever (prodrome) phase ends and during the rash phase

As the lesions scab over, transmission decreases (19)

The smallpox vaccination is a suspended live vaccinederived from vaccinia To prevent bacterial contamination ofthe lyophilized vaccine, polymyxin B, dihydrostreptomycin,chlortetracycline, and neomycin are included in the prepara-tion Other preparations under study include a calf-derivedvaccine and a vaccinia virus grown in monkey kidney andhuman fibroblast cells

Adverse Effects

Live vaccine can cause many adverse effects (20,21) In a masssmallpox vaccination plan, to immunize 75% of the population(aged 1–65), 4600 serious adverse events and 285 deaths willoccur (22)

Pustule formation One of the negative impacts of the

cur-rent smallpox vaccine program has been the realization

that smallpox vaccine causes a noticeable pustulewhen immunization occurs Many people currently be-ing vaccinated have no prior experience with this type

of vaccine We have become accustomed to viral cines that are administered as a “shot”—i.e., influenza,hepatitis, MMR (measles, mumps and rubella), andVZV (chickenpox)—where an adverse effect consists of

vac-a little erythemvac-a vac-and edemvac-a surrounding the injectionsites An open wound, improperly cared for, can becomeinfected or can cause variolation on other body parts.The eyes are particularly sensitive to keratitis from fo-mite transmittal

Allergy to vaccine components or residual immunity.

Presence of a rapidly-forming erythema without ment of the vesicle or pustule may indicate past vaccina-tion immunity and/or allergy to vaccine compounds

develop-Death Approximately one death per million

vaccina-tions occurs These usually occur among infants

Local reactions Most brief symptomatic reactions include

fever, muscle aches, headache, nausea, and/or fatigue

Eczema vaccinatum Where active (or even healed)

eczema/atopic dermatitis occurs, eczema vaccinatumcan occur

Immunocompromised Progressive vaccinia may occur

in patients with depressed cell-mediated immunitywith increased numbers of HIV-positive patients andwidespread use of immunosuppressive drugs

Neurologic implications Post vaccinal

encephalomy-elitis (PVEM) may occur even if there is no cation for vaccination (23) There are few signs of viraldissemination on the vaccine skin site, but neurologicsymptoms may begin in 2–30 days after rash onset Ini-tial complaints are very similar to local reactions re-ported by others except that high fevers and otherneurologic signs occur Seizures are most frequent inchildren Rates of PVEM differ and this is attributedto: 1) strain of vaccinia virus; 2) vaccine preparation; 3)viability of vaccinia virus used; 4) method of vaccinedelivery; and 5) level of post vaccine surveillance (23)

contraindi-Special Considerations

Vaccination of pregnant women There are reported

cases of fetal vaccinia occuring after vaccination ing pregnancy

dur-Coadministration of vaccine immune globin (VIG) with smallpox vaccine VIG may prevent or de-

crease the severity of smallpox Post-exposure tion may also be effective if it is administered with in

vaccina-4 days of known exposure

Exposed persons with vaccine contraindications.

Administration of smallpox vaccine and VIG neously can reduce side effects for those with vaccine con-traindications who are exposed to an infected person (24)

simulta-New Vaccines for Poxviruses Currently under Investigation

Cell culture and recombinant vaccines may produce solid nity with fewer complications Should monkeypox continue to betransmitted from animal reservoirs to humans, there may besome effort to develop a vaccine Fortunately, some immunity tomany of the poxviruses is provided by the smallpox vaccination.One of the positions against destroying the remaining smallpoxcultures is that the smallpox virus, itself, may become the back-bone for a multiple-pox virus that would extend protectionagainst orf, molluscum contagiosum, vaccinia, and other poxvi-ruses Others respond that the manipulated poxvirus strainsare now the most important as they can confer immunity and donot cause disease Obviously, the threat of poxviruses being usedfor terrorism is factored into the decision-making process

immu-MEASLES, MUMPS, AND RUBELLA VACCINES

Measles, mumps, and rubella are described in Chapter 3.Each of these viruses has its own vaccine to be described later.The vaccination for these three classic childhood diseases istypically given as a combination MMR vaccine (Table 4.3).Combination vaccines tend to require fewer total immuniza-tions to achieve a satisfactory efficacy rate, are usually lessexpensive, and provide a greater opportunity to inoculatemasses of people in a short period of time (25)

Table 4.3 Immunization Schedules

Footnotes for Recommended Adult Immunization Schedule

by Age Group and Medical Conditions, United States, 2003–2004

1 Tetanus and diphtheria (Td)—Adults

in-cluding pregnant women with uncertain

histo-ries of a complete primary vaccination sehisto-ries

should receive a primary series of Td A

pri-mary series for adults is 3 doses: the first 2

doses given at least 4 weeks apart and the 3rd

dose, 6–12 months after the second

Adminis-ter 1 dose if the person had received the

pri-mary series and the last vaccination was 10

years ago or longer Consult MMWR 1991; 40

(RR-10): 1–21 for administering Td as

prophy-laxis in wound management The ACP Task

Force on Adult Immunization supports a

sec-ond option for Td use in adults: a single Td

booster at age 50 years for persons who have

completed the full pediatric series, including

the teenage/young adult booster.

Guide for Adult Immunization 3rd ed ACP

1994:20.

2 Influenza vaccination—Medical

indica-tions: chronic disorders of the cardiovascular

or pulmonary systems including asthma;

chronic metabolic diseases including

diabe-tes mellitus, renal dysfunction,

hemoglobin-opathies, or immunosuppression (including

Immunosuppression caused by medications

or by human immunodefidency virus [HIV]),

requiring regular medical follow-up or

hos-pitalization during the preceding year;

women who will be in the second or third

trimester of pregnancy during the influenza

season Occupational indications:

health-care workers Other indications: residents of

nursing homes and other long-term care

fa-cilities; persons likely to transmit influenza to

persons at high-risk (in-home care givers to

persons with medical indications, household

leukemia, lymphoma, multiple myeloma, Hodgkins disease, generalized malignancy, organ or bone marrow transplantation), chemotherapy with alkylating agents, anti- metabolites, or long-term systemic corticos- teroids Geographic/other indications: Alas- kan Natives and certain American Indian populations Other indications: residents of nursing homes and other long-term care fa- cilities.

cy, HIV infection, leukemia, lymphoma, tiple myeloma, Hodgkins disease, generalized malignancy, organ or bone marrow transplan- tation), chemotherapy with alkylating agents, antimetabolites, or long-term system-

mul-ic cortmul-icosteroids For persons 65 and older, one-time revaccination if they were vaccinat-

ed 5 or more years previously and were aged less than 65 years at the time of primary vaccination.

MMWR 1997; 46(RR-8):1–24.

5 Hepatitis B vaccination—Medical

indica-tions: hemodialysis patients, patients who receive dotting-factor concentrates.Occupa- tional indications; health-care workers and public-safety workers who have exposure to blood in the workplace, persons in training

in schools of medicine, dentistry, nursing, lab oratory technology, and other allied health pro contacts and out-of-home caregivers of children

birth to 23 months of age, or children with

asthma or other indicator conditions for

influ-enza vaccination, household members and care

givers of elderly and adults with high-risk

con-ditions); and anyone who wishes to be vaccinated

For healthy persons aged 5–49 years without

high risk conditions, either the inactivated

vac-cine or the intranasally administered influenza

vaccine (Flumist) may be given.

MMWR 2003; 52 (RR-B):1–36; MMWR 2003;

53 (RR-13):1–8.

3 Pneumococcal polysaccharide

vaccina-tion—Medical indications: chronic disorders of

the pulmonary system (excluding asthma),

car-diovascular diseases, diabetes mellitus, chronic

liver diseases including liver disease as a result

of alcohol abuse (e.g., cirrhosis), chronic renal

fail-ure or nephratic syndrome, functional or an

atom-ic asplenia (e.g., satom-ickle cell disease or splenectomy),

fessions Behavioral indications: injecting drug users, persons with more than one sex partner in the previous 6 months, persons with a recently acquired sexually-transmit- ted disease (STD), all clients in STD clinics, men who have sex with men Other indica- tions: household contacts and sex partners

of persons with chronic HBV infection, ents and staff of institutions for the devel- opmentally disabled, international travelers who will be in countries with high

cli-or intermediate prevalence of chronic HBV infection for more than 6 months, inmates

of correctional facilities MMWR 1991; 40

(RR-13):1–19.

(www.cdc.gov/travel/diseases/hby.htm)

6 Hepatitis A vaccination—For the combined

HepA-HepB vaccine use 3 doses at 0, 1, 6 months) Medical indications: persons with immunosuppressive conditions (e.g., congen-

ital immunodeficiency, HIV infection,

dotting-factor disorders or chronic liver disease Behavioral indications: men who have sex with

(continued)

Table 4.3 (Continued)

Footnotes for Recommended Adult Immunization Schedule

by Age Group and Medical Conditions, United States, 2003–2004

men, users of injecting and noninjecting illegal

drugs Occupational indications: persons

work-ing with HAV-infected primates or with HAV

in a research laboratory setting Other

indica-tions: persons traveling to or working in

coun-tries that have high or intermediate

endemicity of hepatitis A.

MMWR 1999; 48 (RR-12):1–37, (www.cdc.gov/

travel/diseases/hav.htm)

7 Measles, Mumps, Rubella vaccination

(MMR)—Measles component: Adults born

be-fore 1957 may be considered immune to

mea-sles Adults born in or after 1957 should receive

at least one dose of MMR unless they have a

medical contraindication, documentation of at

least one dose or other acceptable evidence of

immunity A second dose of MMR is

recom-mended for adults who:

• are recently exposed to measles or in an

of young children, day care employees, and residents and staff members in institutional settings), persons who live or work in envi- ronments where VZV transmission can occur (e.g., college students, inmates and staff members of correctional institutions, and military personnel), adolescents and adults living in households with children, women who are not pregnant but who may become pregnant in the future, international trav- elers who are not immune to infection Note: Greater than 95% of U.S born adults are immune to VZV Do not vaccinate preg- nant women or those planning to become pregnant in the next 4 weeks If pregnant and susceptible, vaccinate as early in post- partum period as possible.

• work in health care facilities

• plan to travel internationally

Mumps component: 1 dose of MMR should be

adequate for protection Rubella component:

Give 1 dose of MMR to women whose rubella

vaccination history is unreliable and counsel

women to avoid becoming pregnant for 4 weeks

after vaccination For women of child-bearing

age, regardless of birth year, routinely

deter-mine rubella immunity and counsel women

re-garding congenital rubella syndrome Do not

vaccinate pregnant women or those planning

to become pregnant in the next 4 weeks If

pregnant and susceptible, vaccinate as early in

postpartum period as possible.

MMWR 1998; 47 (RR-8):1–57; MMWR 2001;

50:1117.

8 Varicella vaccination—Recommended for all

persons who do not have reliable clinical history

of varicella infection, or serological evidence of

varicella zoster virus (VZV) infection who may

be at high risk for exposure or transmission.

and W-135)—Consider vaccination for

per-sons with medical indications: adults with terminal complement component deficien- cies, with anatomic or functional asplenia Other indications: travelers to countries in which disease is hyperendemic or epidemic (*meningitis belt* of sub-Saharan Africa, Mecca, Saudi Arabia for Hajj) Revaccina- tion at 3–5 years may be indicated for per- sons at high risk for infection (e.g., persons residing in areas in which disease is epidem- ic) Counsel college freshmen, especially those who live in dormitories, regarding meningococcal disease and the vaccine so that they can make an educated decision

about receiving the vaccination MMWR

2000; 49 (RR-7):1–20.

Note: The AAFP recommends that colleges

should take the lead on providing education

on meningococcal infection and vaccination and offer it to those who are interested Phy- sicians need not initiate discussion of the meningococcal quadravalent polysaccharide vaccine as part of routine medical care.

(continued)

Table 4.3 (Continued)

Recommended Adult Immunization Schedule

by Age Group and Medical Conditions United States, 2003–2004

Summary of Recommendations Published by

The Advisory Committee on Immunization Practices

Department of Health and Human Services

Centers for Disease Control and Prevention

(continued)

Table 4.3 (Continued)

This schedule indicates the recommended ages for routine administration of currently licensed childhood vaccines, as of December 1, 2003, for children through age 18 years Any dose not given at the recommended age should be given at any subsequent visit when indicated and feasible Indicates age groups that warrant special effort to administer those vaccines not previously given Additional vaccines may be licensed and recommended during the year Licensed combination vaccines may be used whenever any components

of the combination are indicated and the vaccine’s other components are not contraindicated Providers should consult the manufacturers’ package inserts for detailed recommendations Clinically significant adverse events that follow immunization should be reported to the Vaccine Adverse Event Reporting System (VAERS) Guidance about how to obtain and complete a VAERS form can be found on the internet: http://www.vaers.org/ or by calling 1-800-822-7967.

1 Hepatitis B (HepB) vaccine All infants should

receive the first dose of hepatitis B vaccine soon

affer birth and before hospital discharge; the first

dose may also be given by age 2 months if the

infant’s mother is hepatitis B surface antigen

(HBsAg) negative Only monovalent HepB can be

used for the birth dose Monovalent or

combination vaccine containing HepB may be

used to complete the series Four doses of vaccine

may be administered when a birth dose is given

The second dose should be given at least 4 weeks

after the first dose, except for combination

vaccines which cannot be administered before age

6 weeks The third dose should be given at least

16 weeks after the first dose and at least

8 weeks after the second dose The last does in the

vaccination series (third or fourth dose) should

not be administered before age

24 weeks.

Infants born to HBsAg-positive mothers

should receive HepB and 0.5 mL of Hepatitis B

Immune Globulin (HBIG) within 12 hours

of birth at separate sites The second dose is recommended at age

1 to 2 months The last dose in the immunization series should not be administered before age 24 weeks These infants should be tested for HBsAg and antibody to HBsAg (anti-HBs) at age 9 to

15 months.

Infants born to mothers whose HBsAg status is unknown should receive the first dose of the HepB series within 12 hours of birth Maternal blood should be drawn as soon as possible to determine the mother’s HBsAg status; if the HBsAg test is positive, the infant should receive HBIG as soon as possible (no later than age 1 week) The second dose is recommended at age

1 to 2 months The last dose in the immunization series should not be administered before age 24 weeks.

(continued)

Recommended Childhood and Adolescent Immunization

Schedule – United States, January − June 2004

Range of Recommended Ages Catch-up Immunization Preadolescent Assessment

Vaccine Age Birth 1 mo 2 mo 4 mo 6 mo 12 mo 15 mo 18 mo 24 mo 4−6 y 11−12 y 13−18 y

Vaccines below this line are for selected populations

Hib Hib Hib3 Hib

MMR #2 MMR #1

Varlcella MMR #2

HepB series

Td Td

Table 4.3 (Continued)

2 Diphtheria and tetanus toxoids and

acellular pertussis (DTaP) vaccine

The fourth dose of DTaP may be

administered as early as age 12 months,

provided 6 months have elapsed since the

third dose and the child is unlikely to

return at age 15 to 18 months The final

dose in the series should be given at age

≥4 years Tetanus and diphtheria toxoids

(Td) is recommended at age 11 to 12 years

if at last 5 years have elapsed since the

last dose of tetanus and diphtheria

toxoid-containing vaccine Subsequent routine Td

boosters are recommended every 10 years.

3 Haemophilus Influenzae type b (Hib)

conjugate vaccine Three Hib conjugate

vaccines are licensed for infant use If

PRP-OMP (PedvaxHIB or ComVax [Merck] is

administered at ages 2 and 4 months, a

dose at age 6 months is not reqeired DTaP/

Hib combination products should not be

used for primary immunization in infants

at ages 2, 4 or 6 months but can be used

as boosters following any Hib vaccine The

find dose in the series should be given at

age ≥12 months.

4 Measles, mumps, and rubella vaccine

(MMR) The second dose of MMR is

recommended routinely at age 4 to 6 years

but may be administered during any visit,

provided at least 4 weeks have elapsed

since the first dose and both doses are

administered beginning at or after age

12 months Those who have not previously

received the second dose should complete

the schedule by the 11- to 12-year-old visit.

5 Varicella vaccine Varicella vaccine is

recommended at any visit at or after age

12 months for susceptible children (i.e.,

those who lack a reliable history of

chickenpox) Susceptible persons age ≥13

years should receive 2 doses, given at least

4 weeks apart.

6 Pneumococcal vaccine The heptavalent

pneumococcal conjugate vaccine (PCV) is

recommended for all children age 2 to 23

months It is also recommended for certain

children age 24 to 59 months The final dose

in the series should be given at age ≥12 months Pneumococcal polysaccharide vaccine (PPV) is recommended in addition

to PCV for certain high-risk groups See

MMWR 2000;49(RR-9):1–38.

7 Hepatitis A vaccine Hepatitis A vaccine

is recommended for children and adolescents

is selected states and regions and for certain high-risk groups; consult your local public health authority Children and adolescents

in these states, regions, and high-risk groups who have not been immunized against hepatitis A can begin the hepatitis A immunization series during any visit The 2 doses in the series should be administered

at least 6 months apart See MMWR

1999;48(RR-12):1–37.

8 Influenza vaccine Influenza vaccine is

recommended annually for children age ≥6 months with certain risk factors (including but not limited to children with asthma, cardiac disease, sickle cell disease, human immunodeficiency virus infection, and diabetes; and household members of

persons in high-risk groups [see MMWR

2003;52 (RR-8):1–36]) and can be administered to all others wishing to obtain immunity In addition, healthy children age 6 to 23 months are encouraged

to receive influenza vaccine if feasible, because children in this age group are at substantially increased risk of influenza- related hospitalizations For healthy persons age 5 to 49 years, the intranasally administered live-attenuated influenza vaccine (LAIV) is an acceptable alternative

to the intramuscular trivalent inactivated

influenza vaccine (TIV) See MMWR

2003;52(RR-13):1–8 Children receiving TIV should be administered a dosage appropriate for their age (0.25 mL if age 6 to 35 months or 0.5 mL if age

≥3 years) Children age ≤ 8 years who are receiving influenza vaccine for the first time should receive 2 doses (separated by

at least 4 weeks for TIV and at least 6 weeks for LAIV).

For additional information about vaccines, including precautions and contraindications for immunization and vaccine shortages, please visit the National Immunization Program Web site at www.cdc.gov/nip/ or call the National Immunization Information Hotline at 800-232-2522 (English) or 800-232-0233 (Spanish)

Approved by the Advisory Committee on Immunization Practices (www.cdc.gov/nip/ acip), the American Academy of pediatrics (www.aap.org), and the American Academy of Family Physicians (www.aafp.org).

(continued)

to your state or local health department.

Table 4.3 (Continued)

See Footnotes for Recommended Adult Immunization Schedule, by Age Group and Medical

Conditions United States, 2003–2004 on back cover For all persons Catch-up on For persons with medical/

in this group childhood vaccinations exposure indications

* Covered by the Vaccine injury Compensation Program For Information on how to file a claim call 800-338-2382 Please also disit www.hrq.gov/otp/vicp To file a claim for vaccine injury contact: U.S Court of Federal Claims,

717 Madison Place, H.W., Washington D.C 20005, 202-219-9657.

This schedule indicates the recommended age groups for routine administration of currently licensed vaccines for persons 19 years of age and older Licensed combination vaccines may be used whenever any components of the combination are indicated and the vaccines other components are not contraindicated Providers should consult the manufactures’ package inserts for detailed recommendations.

Report all clinically significant post-vaccination reactions to the Vaccine Adverse Event Reporting System (VAERS) Reporting forms and instructions on filing a VAERS report are available by calling 800-822-7967 or from the VAERS website at www.vaers.org.

For additional information about the vaccines listed above and contraindications for immunization, visit the National Immunization Program Website at www.cdc.gov/nip/ or call the National Immunization Hotline at 800- 232-2522 (English) or 800-232-0233 (Spanish).

Approved by the Advisory Committee on Immunization Practices (ACIP), and accepted by the American College

of Obstetridans and Gynecologists (ACOG) and the American of Family Physicians (AAFP)

19 −49 Years 50 −64 Years 65 Years and older

1 does booster every 10 years 1

1 dose annually2 1 dose annually2

1 dose if measies, mumps, or rubelia

vaccination history is unraliable;

2 doses for persons with

occupa-ssional or other indications 7

Table 4.3 (Continued)

See Special Notes for Medical Conditions below—also see Footnotes for Recommended Adult Immunization Schedule, by Age Group and Medical Conditions United States, 2003-2004 on back cover

For all persons Catch-up on For persons with medical/ Contraindicated

in this group childhood vaccinations exposure indications

Special Notes for Medical Conditions

A For women without chronic diseases/conditions,

vaccinate If pregnancy will be at 2 nd or 3 rd trimester

during influenza season For women with chronic

deseases/conditions, vaccinate at any time during

the pregnancy.

B Although chronic liver disease and alcoholism are

not indicator conditions for influenza vaccination,

give 1 dose annually if the patent is ≥50 years, has

other indications for influenza vaccine, or if the

patient requests vaccination.

C Asthma a is an indication condition for influenza

but not for pneumococcal vaccination.

D For all persons with chornic liver disease.

E For persons < 65 years revaccinate once after 5

years or more have elapsed since initial

vaccination.

F Persons with impaired humoral immunity but

intact cellular immunity may be vaccinated,

MMWR 1999;48 (RR-06):1–5.

G Hemodialysis patients: Use special formulation of

at one site Vaccinate early in the course of renal disease Assess antibody iters to hep B surface antigen (anti-HBs) levels annually Administer additional doses if anti-HBs levels decline to < 10 milliinternational units (mlU)/mL.

H There are no data specially on risk of severe or complicated influenza infections among persons with asplenia However, Influenza is a risk factor for secondary bacterial infections that may cause severe disease in asplenics.

I Administer meningococcal vaccine and consider Hib vaccine.

J Elective splenectomy: vaccinate at least 2 weeks before surgery.

K Vaccinate as close to diagnosis as possible when CD4 cell counts are highest.

L Withhold MMR or other measles containing vaccines from HIV-infected persons with evidence of severe

coccal (polysacch- aride)3,4

Varicallaa,8

Pregnancy

Diabetes, heart disease,

chronic pulmonary disease,

chronic liver disease,

including chronic alcoholism

Congenltal immunodeficiancy,

leukamia, lymphoma, generalized

malignancy, therapy with alkylating

agents, antimatabolites, radiation or

large amounts of cortlcosterolds

Renal failure / and stage renal

Live virus vaccines for measles, mumps, rubella wereintroduced in the 1960s and, after widespread implementa-tion in the United States, annual reported cases of these infec-tions declined by more than 98% (26) The most recentrecommendations by the Centers for Disease Control and Pre-vention (CDC) suggest vaccination with the first MMR dose at12–15 months and the second dose at 4–6 years of age (27).Two doses confer 92% immunity, which is sufficient to preventepidemics.

Special Considerations

Pregnancy Because these vaccines consist of live

atten-uated viruses, they should not be administered to nant women or those planning to become pregnant inthe next 3 months The theoretical risk of congenitalrubella syndrome after immunization has been the pri-mary concern However, a study of 321 women who hadreceived the rubella vaccine 3 months before or afterconception revealed no congenital malformations com-patible with congenital rubella infection (27)

preg-Immunosuppressed Immunization is also

contraindi-cated in immunosuppressed patients, although it can beadministered to individuals with asymptomatic HIV in-fection as well as persons with mild immunosuppression

Healthy individuals In healthy individuals, minor

ill-nesses with or without fever are not a contraindication

to vaccination

Patients with a history of anaphylactic tivity to neomycin These persons should not receive

hypersensi-the MMR vaccine

Egg allergy The vaccine can be administered to patients

with an allergy to eggs, since the risk for severe lactic reactions is exceedingly low (28,29) It is recom-mended that these patients be observed for 90 minutesafter immunization (29) Khahoo and Loch (28) reportthat most severe cardiorespiratory allergic reactionswere reported in children who were most likely allergic

anaphy-to the gelatin or neomycin in the vaccine rather thanovalbumin

Measles virus has been noted to be the most infectious disease

of humankind, in terms of the minimal number of virions essary to produce infection (30) An estimated 75% of suscep-tible family contacts who are exposed to a case of measlesdevelop the disease (31) Because humans are the only reser-voir for measles virus, global eradication is technically feasi-ble A meeting cosponsored by the World Health Organization,CDC, and the Pan American Health Organization convened in

nec-1996 and adopted the goal of global eradication by a targetdate during 2005–2010 (32) Due to universal childhoodimmunization in the United States, measles is no longer con-sidered an indigenous disease in this country In 2001, a total

of 116 confirmed measles cases were reported—54 tionally imported and 62 indigenous (37 import linked and 25unknown sources) In 2002, a total of only 37 cases of measleswere confirmed, which represents a record low number ofreported cases It is important, however, to guard against com-placency with these encouraging figures In 2003, 39 cases hadbeen confirmed by August, which should serve as a reminder

interna-of the continuing need for vaccination (33)

Lack of compliance with routine MMR vaccination in thepast led to a resurgence of measles infection in the UnitedStates from 1989–1991, with some deaths reported (32) More-over, greater than 1 million children die of measles each year

in Third World countries (34) The current measles vaccine is

a further attenuated version of the live preparations ously available, resulting in fewer adverse reactions in recipi-ents It is produced by culturing the Moraten virus strain inchick embryo cells Measles vaccination produces a mild orinapparent infection which is noncommunicable Both humoraland cellular immune responses develop as a result (35) Afterreceiving two doses of vaccine, 95–99% of recipients developserologic evidence of immunity to measles (36,37) Immunity

previ-is thought to be life-long, similar to that acquired after infectionwith the wild-type virus (38) Measles infection has rarely beenreported in patients with previously documented postimmuni-zation seroconversion (39,40) In a recent measles outbreak in

Campania, Italy, low vaccination rates (76%) were cited as themain cause (41)

Adverse Effects

Adverse effects after measles vaccination are typically mild

Fever Five to 15 percent of recipients develop a fever of

days after immunization (42) These individuals arelargely asymptomatic, but some may develop a tran-sient viral exanthem (26)

Encephalitis An associated encephalitis or

encephalop-athy has rarely been reported after immunization, andoccurs in less than 1 per 1 million vaccinees (43)

Subacute sclerosing panencephalitis There have

been early concerns about the association of measlesvaccination and subacute sclerosing pancencephalitis(SSPE), since this complication may occur with naturalinfection A small number of reports have describedthe occurrence of SSPE in persons with a history ofvaccination but no known history of infection (44–46).More recent evidence indicates that at least some ofthose cases had unrecognized natural measles infec-tion prior to vaccination, and the SSPE was directlyrelated to the infection (27) Widespread measles im-munization has nearly eliminated SSPE in the UnitedStates, and the live measles vaccine does not increasethe risk for this complication (27)

More recently, the measles vaccine has been administered as

an aerosolized vaccine Aerosol administration has fewer sideeffects than injection inoculation Immunogenicity is superior

in the aerosol administration when compared with traditionalinjections Thus the potential efficacy and cost warrant fur-ther studies of aerosol measles immunizations (47)

Mumps

The live attenuated mumps vaccine (Jeryl-Lynn strain) is pared in chick embryo cell culture Immunization produces a

pre-mild subclinical infection that is noncommunicable Earlyclinical studies have shown that 97% of children and 93% ofadults develop serological evidence of immunity after vaccina-tion (48–50) Outbreak-based studies, however, have reportedlower efficacy rates, ranging from 75–95% protection frominfection (51–54) Although the duration of immunity in vac-cine recipients is not completely known, serologic and epide-miologic evidence suggests that immunity persists for at least

30 years (55–58)

Adverse Effents

Adverse reactions are generally mild and uncommon aftermumps vaccination

Fever, parotitis, and exanthem Low-grade fever, mild

parotitis, and a viral exanthem have been reported

Neurological effects Serious reactions such as adverse

neurological effects are extremely rare and have notbeen causally associated with the mumps vaccine (59)

Rubella

Three different live attenuated rubella vaccine strains wereinitially developed and licensed in the United States Thesewere all replaced in 1979 by the RA 27/3 (rubella abortus 27,explant 3) vaccine which is grown in human diploid fibroblastcell culture This vaccine produces nasal antibodies as well ashigher and more persistent antibody titers, which bettermimic the immune protection developed after natural infec-tion (60,61)

Vaccination induces an antibody response in more than97% of recipients (49,62) Immunity in vaccine recipients isthought to be lifelong, and has been shown to persist for atleast 16 years (63,64)

Adverse Effects

Adverse effects after rubella vaccination are typically mild

Fever, lymphoadenopathy, or exanthem 5–15% of

vaccinated children develop fever, lymphadenopathy,

or a viral exanthem, typically between 5–12 days aftervaccination (50,65)

Arthralgia /arthritis Arthralgias and arthritis are a

frequent complication in adult vaccinees, particularlywomen, and may develop in 25–40% of this populationgroup (66–68) Occurrences in children are rare (0.5%)(66) These joint symptoms typically begin within thefirst 3 weeks after vaccination and remit within 11days The knees and the fingers are most frequently in-volved, but any joint may be affected (67)

Special Considerations

Pregnancy and vaccination rates Failure to achieve

50–60% immunity to rubella by vaccination leaveswomen of childbearing age susceptible to developingrubella infection during pregnancy This often causescongenital rubella in children born of mothers who con-tract rubella during early pregnancy For example, ru-bella immunization in Greece was classed as “optional,”but less than 50% of the children were vaccinated Anepidemic in Greece in 1993 affected more women ofchildbearing age than ever before This, in turn, wasfollowed by the births of the largest number of babieswith congenital rubella ever recorded in Greece (69)

VARICELLA-ZOSTER VIRUS VACCINE

Prior to the widespread availability of varicella vaccine, yearlyU.S figures for varicella disease included approximately 4million cases, 11,000 hospitalizations, and 100 deaths (70).The currently available varicella vaccine in the United States

is a live-attenuated Oka strain vaccine approved in 1995 Thevaccine is very safe and effective (71–73) Clinical trials beganover 20 years earlier in Japan after the vaccine was developed

by attenuation of virus isolated from the vesicular fluid of

a healthy boy (with the surname Oka) with natural cella infection (74) These initial studies showed a 90% serocon-version rate 4 weeks after vaccination with few clinical

vari-reactions (75) Follow-up studies showed that the vaccine tected against chickenpox for at least 17–19 years, and all ofthe subjects had persistent antibodies and delayed-type skinreactions to the varicella-zoster antigen (76) In the UnitedStates, a double-blind, placebo-controlled study of the Okavaccine in 914 children revealed an efficacy of 100% at 9 months(77) After a seven-year follow-up, 95% of the subjects remainedfree of clinical disease with chickenpox (78) Compared withthe disease rates of unvaccinated children in the UnitedStates, it appears that the Oka vaccine reduces the rate ofvaricella in children participating in the clinical trials by65–90% (74) Additional studies in the United States haveshown that the Oka vaccine induces humoral and cell-mediatedimmunity in healthy children (79–81), both of which havebeen demonstrated to persist for at least 8 years (82) Delayed-type hypersensitivity skin reactions to varicella-zoster virusantigens have also been shown to occur for at least 10 yearsafter vaccination (83)

pro-Studies of adolescents and adults have demonstratedthat 2 doses 4–8 weeks apart were necessary to produce sero-conversion rates and antibody responses similar to thoseobtained in healthy children (84) Vaccination is recommendedfor susceptible adults, particularly those in high-risk situa-tions (health-care personnel, etc.) The vaccine is recom-mended for all children who have no history of chickenpox and

is required to attend school in most states Clinical studieshave also evaluated the use of vaccination in immunosup-pressed children and adolescents, particularly in those withacute lymphocytic leukemia (85–87) Results indicated thatvaccination is safe for those who are at least 1 year away frominduction chemotherapy if the current chemotherapy is haltedaround the time of vaccination and the patient’s lymphocyte

individ-uals is lower than that of healthy recipients, thus requiring

2 doses separated by 3 months Transmission of varicella fromthese vaccinees may occur if a vaccine-associated rash develops,although the risk of transmission is about one-fourth that ofnatural varicella (20–25% vs 87%) (88) The Oka vaccine should

be given as a single dose to children 12 months to 12 years