Immunizations and Travel

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Contents 1 Immunizations and Travel 1.1 GENERAL CONSIDERATIONS 1.1.1 Principles of Vaccination 1.1.2 Records, Route, Site, and Dosage 1.1.3 Vaccine Schedules and Missed Doses 1.1.4 Multiple Vaccines and Immune Globulins 1.1.5 Hypersensitivity and Local Reactions 1.2 GENERAL RECOMMENDATIONS 1.3 SPECIAL RECOMMENDATIONS 1.3.1 Pregnancy and Breast-feeding 1.3.2 Immunocompromise and Other High-Risk Medical Conditions 1.3.3 Human Immunodeficiency Virus Infection. 1.3.4 Severe Immunocompromise Without HIV Infection. 1.3.5 Lifestyle and Environmental Risk 1.3.6 Occupational Risk 1.3.7 Students 1.3.8 Immigrants and Refugees 1.4 VACCINE-PREVENTABLE ILLNESSES, VACCINES, AND POSTEXPOSURE PROPHYLAXIS 1.4.1 Tetanus and Diphtheria 1.4.2 Measles, Mumps, and Rubella 1.4.3 Measles. 1.4.4 Mumps. 1.4.5 Rubella. 1.4.6 Vaccine. 1.4.7 Prophylaxis. 1.4.8 Varicella 1.4.9 Hepatitis B 1.4.10 Hepatitis A 1.4.11 Pneumococcus 1.4.12 Influenza 1.4.13 Hemophilus Influenza b 1.4.14 Meningococcus 1.4.15 Lyme Disease 1.4.16 Rabies 1.4.17 Poliomyelitis 1.4.18 Typhoid 1.4.19 Yellow Fever 1.4.20 Japanese Encephalitis 1.4.21 Cholera 1.4.22 Plague, Anthrax, Vaccinia, and Bacille Calmette-Guérin 1.5 TRAVEL 1.6 ADDITIONAL READINGS

[edit] Immunizations and Travel

Julie Kaufmann

Immunizations are one of the most cost-effective medical interventions for an individual and the public health. Although the prevention of disease in an individual is readily achievable, the ultimate goal is the elimination of disease by maintaining a high level of immunity in the population. Unfortunately, immunizations are not a part of routine care in many adult medicine practices. As a result, a substantial proportion of the morbidity and mortality from vaccine-preventable diseases occurs in older adolescents and in adults.

[edit] GENERAL CONSIDERATIONS

The recommendations for vaccinations in the United States come from the Advisory Committee on Immunization Practices (ACIP). The American College of Physicians also publishes guidelines. Recommendations are based on an individual's risk of exposure to the disease, susceptibility to the disease, and the risk of transmitting the disease to others. The characteristics of the immunobiologic (vaccine or immune globulin), scientific knowledge about the principles of immunization, and the risk, benefit, and cost of the immunobiologic are also considered.

Most vaccine-preventable illnesses and disease exposures requiring postexposure prophylaxis must be reported to the local or state health department. Public health officials rely on the reporting of vaccine-preventable illnesses to evaluate and plan prevention strategies on a local level. In addition, the data are used to evaluate national policies, practices, and strategies for future vaccination programs.

[edit] Principles of Vaccination

Active immunization uses immunogens to simulate a natural infection, which results in an antitoxic, antiinvasive, or neutralizing activity in the recipient. Such immunogens include live attenuated virus, inactivated virus, and bacterial proteins or polysaccharides. Some agents induce lifelong protection, some provide partial protection, and some must be readministered for continued effectiveness. The efficacy of the vaccine is defined by the protection against natural disease. The antibody response is an indirect measure of protection because in some cases the immunologic reaction responsible for protection is poorly understood; in this instance the serum antibody concentrations are not always predictive of protection.

Passive immunization with immune globulin (IG) is used (1) to provide immediate antibody levels for individuals who have recently been exposed or who soon may be exposed to a disease; (2) to provide antibody for individuals who are immunocompromised and would be expected to have a poor immunogenic response to an illness exposure or to a previous active immunization; or (3) to help suppress the effects of a toxin when a disease is already present. Pooled IG is derived from a large pool of donors so is likely to contain antibodies to hepatitis A and measles. The disease-specific immune globulins HBIG, TIG, HRIG, and VZIG are derived from selected donor pools with high titers to the desired antibody (Box 5-1).

Box 5-1 - Agencies and Abbreviations

Agencies Morbidity and Mortality Weekly Report (MMWR) http://www2.cdc.gov/mmwr US Department of Health and Human Services Public Health Service Centers for Disease Control and Prevention (CDC) National Center for Prevention Services Division of Quarantine Atlanta, GA 30333 1-404-639-3311 http://www.cdc.gov/nip Traveler's hotline: CDC 1-404-332-4559 http://www.cdc.gov (select traveler's health) Vaccine Adverse Event Reporting System (VAERS) PO Box 1100 Rockville, MD 20849-1100 1-800-822-7967 http://www.cdc.gov/nip/VAERS.htm Abbreviations ACIP Advisory Committee on Immunization Practices WHO World Health Organization Td tetanus and diphtheria vaccine MMR measles, mumps, and rubella vaccine IPV inactivated poliovirus vaccine HBV hepatitis B vaccine HAV hepatitis A vaccine HbCV hemophilus influenza(Haemophilus influenzae) b conjugate vaccine IG immune globulin HBIG hepatitis B IG VZIG varicella-zoster IG TIG tetanus IG HRIG human rabies IG

[edit] Records, Route, Site, and Dosage

Physicians should maintain a permanent vaccination record for each patient as required by law. This record should include type of immunization, site and route of vaccination, lot number and expiration date, and date given. Patients should be given information on the risks and benefits of immunization and a copy of their own vaccination record for future reference.

The route of immunization is important for each vaccine. Vaccines developed for intramuscular (IM) use should not be given subcutaneously because the immune response may be decreased, and risks include local irritation, inflammation, and necrosis from the adjuvant in the vaccine. The preferred site for adult IM injections is the deltoid muscle, where the risk of vascular and neural injury is low. It is preferable to avoid giving two IM injections in the same limb, especially if one is known to cause a local reaction. Except for the administration of large doses of IG, the buttock should not be used routinely as a site for IM injection because of proximity of the sciatic nerve and because the depth of fat may make performing a true IM injection difficult. If the buttock must be used to accommodate large-volume injections (e.g., IG) or multiple doses of vaccines, the upper outer quadrant is preferred. In general, no more than 5 ml should be given at one site.

If it is necessary to give more than one vaccine in a limb, the vaccine sites should be at least 1 to 2 inches (2.5 to 5 cm) apart. Whenever administering any vaccine with an IG, the sites chosen should be remote from each other (e.g., deltoid for vaccine, buttock for IG).

When pooled IG is indicated and IM injections are contraindicated, such as in patients with severe thrombocytopenia or severe coagulation disorder (e.g., hemophilia), an intravenous preparation can be used at a dosage of 110 mg/kg. Because intravenous IG preparations are derived from smaller donor pools, they may not be as effective for hepatitis A or measles prophylaxis, and their efficacy for these purposes is unknown.

In adults a 20-to 25-gauge, 1-to 1½-inch needle is used for IM injections (care should be taken to perform a true IM injection in obese patients); a 23-to 25-gauge, ⅝- to⅝-to ¾-inch needle for subcutaneous injections; and a 25-to 27-gauge, ⅜- to⅜-to ¾-inch needle for intradermal injections.

[edit] Vaccine Schedules and Missed Doses

The recommendations for the dosage of vaccines are derived from clinical experience, experimental trials, and theoretic considerations. Adherence to the recommended schedules provides the most predictable outcome in terms of side effects and clinical efficacy. If a dose is delayed during a vaccination series, the schedule should be continued and not restarted, since generally no decline occurs in final antibody levels. Giving doses at less than the recommended interval, however, should be avoided because it may weaken the immune response, and some vaccines are more likely to produce local or systemic symptoms if given too soon. If a vaccine is given earlier than the recommended time interval, it should not be considered part of a series.

Minor illness with or without fever is not a contraindication to receiving a vaccine, especially if poor compliance is a concern. Moderate or severe illness with or without fever is a contraindication. Vaccination should be delayed, if possible, so that symptoms of the illness are not mistaken for side effects of the vaccine, and to ensure an optimum immune response to the vaccine.

[edit] Multiple Vaccines and Immune Globulins

The administration of multiple vaccines is often desirable to minimize patient visits for vaccination and increase compliance, especially if patient follow-up is uncertain. It may also be necessary if several vaccinations are needed in a short time in preparation for travel abroad. Table 5-1 summarizes recommendations for the simultaneous and nonsimultaneous administration of immunobiologics. If the recommended time intervals cannot be followed, serologic testing should be performed or the second vaccination repeated subsequently.

Table 5-1 Administration of Multiple Vaccines

Modified from CDC: General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR 43(RR-1):15 and 16, 1994.

Vaccine combination	Recommended minimum interval between doses
Two or more killed vaccines	None. May be administered simultaneously or at any interval between doses. (If possible cholera, parenteral typhoid and plague vaccines should be given on separate occasions to avoid accentuating their side effects.)
Killed and live vaccines	None. May be administered simultaneously or at any interval between doses. (Cholera vaccine with yellow fever vaccine is the exception. These vaccines should be given separately at least 3 weeks apart, or antibody response to each may be suboptimal.✢)
Two or more live vaccines✢	May be administered simultaneously. If given separately, they must be separated by at least 4 weeks. Oral typhoid vaccine can be administered at any time before, with, or after parenteral live vaccines.
Live vaccine and purified protein derivative (PPD)✢	May be administered simultaneously. If given separately, PPD should be given 4 to 6 weeks after live vaccine.

✢If guidelines for time intervals cannot be followed, vaccine should be repeated after appropriate interval, or vaccine antibody titers should be measured.

IG preparations and other antibody-containing blood products do not interfere with the immune response to inactivated vaccines, but they do interfere with the antibody response to live vaccines, with the exception of oral typhoid and yellow fever vaccine. Since the immune response to a live vaccine occurs 1 to 2 weeks after vaccination, any IG-containing product should be given 2 weeks after an MMR or 3 weeks after varicella vaccine. The time interval between administering an IG-containing product and then a measles-containing vaccine appears to be dose dependent. The suggested intervals are based on the interference of the immune response to measles vaccine for 5 months after a dose of 80 mg/kg of IG (half-life about 30 days). In general the ranges and intervals are as follows: for up to 10 mg IG/kg, wait 3 months; for 20 mg IG/kg, 4 months; 25 to 50 mg IG/kg, 5 months; 60 to 100 mg IG/kg, 6 months; 160 mg IG/kg, 7 months; 400 mg IG/kg, 8 months; 1000 mg IG/kg, 10 months; and for 2000 mg IG/kg, wait 11 months. Packed red blood cells have an estimated 60 mg IG/kg, and platelet products have 160 mg IG/kg. For simplicity, the CDC recommends waiting 5 months after any IG-containing product and the administration of varicella vaccine. If a live vaccine must be administered within the recommended interval, serologic testing should be performed to ensure an adequate response, or the vaccination should be repeated after the appropriate interval.

[edit] Hypersensitivity and Local Reactions

Some vaccines contain small amounts of antibiotics, preservatives, and animal protein that may induce hypersensitivity reactions (see Contraindications in Table 5-2). Any person with a known anaphylactic response to these components should not receive the vaccine. Most often an allergy to neomycin is not an anaphylactic response but a contact dermatitis. This cell-mediated response is not a contraindication for vaccines containing neomycin. Some vaccines (e.g., tetanus/diptheria, varicella, parenteral typhoid, cholera, plague) typically cause fever, local redness, and soreness. These reactions appear to be toxic rather than hypersensitive. If an urticarial reaction to any vaccine is noted or if a person has a history of a hypersensitivity reaction to a vaccine component, the recipient should have skin testing before a decision is made to continue or discontinue the vaccine.

Table 5-2 Immunizations for Adults in the United States 18 Years of Age and Older

Modified and updated from CDC: Update on adult immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR 40(RR-12):60-66 and 82-86, 1991.

Name	Primary schedule and booster(s)	Indications✢	Side effects	Contraindications✢	Pregnancy†
Tetanus and diphtheria adsorbed toxoid (Td)	Two 0.5-ml IM doses 1 month apart; third dose 6-12 months after second; booster every 10 years (see Table 5-4 for postexposure prophylaxis).	All adults; check for receipt of primary series in refugees, immigrants, and foreign-born patients.	Local erythema and pain; rarely, anaphylaxis, neuropathy encephalitis, Guillain-Barré syndrome.	Neurologic or anaphylactic reaction to previous dose (can be given TIG for postexposure prophylaxis).	Use if indicated; no confirmed risk to fetus.
Measles (as MMR) live virus	One 0.5 ml SC dose; second dose at least 1 month later (or immunity by antibody titer or physician-diagnosed measles).	Adults born after 1956 need one dose; additional dose on entering school, long-term correctional facility, or health care work; during outbreaks; and for foreign travel. Adults born before 1957 are considered immune, but giving one dose to health care workers at risk of exposure may be prudent.	Local erythema and pain, low-grade fever, rash, arthralgias 1 to 21 days after vaccination; rarely, high fever 5-12 days after vaccination; extremely rarely, anaphylaxis and thrombocytopenia within 2 months.	Anaphylaxis to chicken eggs, gelatin, neomycin, or previous dose.	Contraindicated, but no confirmed risk to fetus.
Mumps (as MMR) live virus	One 0.5-ml SC dose (or immunity by antibody titer or physician-diagnosed mumps).	All adults born after 1956. Adults born before 1957 are considered immune.	As for measles.	As for measles.	As for measles.
Rubella (as MMR) live virus	One 0.5-ml SC dose (or immunity by antibody titer).	Adults born after 1956; women of childbearing potential.	As for measles.	As for measles. Rubella vaccine from human diploid cells can be given to persons with anaphylaxis to chicken eggs.	As for measles.
Varicella live virus	Two 0.5-ml SC doses separated by 1 or 2 months (or immunity by reported illness or antibody titers).	All adults.	Typically, local pain and erythema; occasionally fever and varicella-like rash; rarely, zoster.	Anaphylaxis to gelatin, neo-mycin, or previous dose.	Contraindicated —unknown risk to fetus
Hepatitis B recombinant DNA–derived surface antigen particles	Two 1.0-ml IM doses 1 month apart; third dose 5 months after second; higher dose and more frequent schedule for persons with chronic renal failure or immunocompromise. Engerix also approved for dosing at 0, 1, 2, and 12 months to give three doses for upcoming exposure.	Persons with multiple sex partners or sexually transmitted diseases; male homosexuals; injection drug users, persons whose sex partner is in high-risk group; frequent recipients of blood products; hemodialysis patients; health care or public safety workers with frequent blood or body fluid exposures; institutionalized, developmentally disabled patients and their staff; household and sexual contacts of chronically infected carriers (for contacts of acutely infected persons, see Table 5-5); certain travelers to high-risk areas. Consider for persons from endemic area residing in U.S. community with similar culture.	Local erythema and pain; rarely, fever; extemely rarely, anaphylaxis.	Anaphylactic reaction to common baker's yeast, thimerosal, or previous dose.	Use if indicated; no reported risk to fetus.
Hepatitis A inactivated virus	Two 1.0-ml IM doses given 6 to 12 months apart.	Male homosexuals, bisexuals, injection drug users, persons with chronic liver disease or frequently receiving clotting factor concentrates, certain travelers to high-risk areas.	Local erythema and pain; headache, malaise.	Severe reaction to previous dose.	Use if indicated; unknown risk to fetus.
Pneumococcal bacterial polysaccharide	One 0.5-ml IM or SC dose; single revaccination after 5 years for persons with functional or anatomic asplenia, chronic renal failure, nephrotic syndrome, organ transplants, HIV, or severe immunocompromise and for those vaccinated 5 years ago when younger than 65 years and now older than 65 years.	Persons 65 years and older; patients with chronic pulmonary (except asthma) or cardiovascular disease, diabetes, alcoholism, cirrhosis, chronic renal failure, nephrotic syndrome, organ transplantation, asplenia, or immunocompromise from any cause; homeless persons, Native Alaskans; Apache Native Americans.	Local erythema and pain; low-grade fever.	More severe local reactions in persons revaccinated in less than 24 months; anaphylaxis to previous dose or any vaccine component.	Use if indicated; unknown risk to fetus.
Influenza inactivated virus	One 0.5-ml IM dose, seasonally.	As for pneumococcal vaccine (except Native Americans); asthmatic patients, caregivers and household contacts of vaccine candidates, health care workers, any adult desiring to reduce risk, travelers to tropics or southern hemisphere at risk of poor outcome.	Local pain and erythema; malaise; low-grade fever; headache.	Severe reaction to previous dose; anaphylaxis to chicken eggs.	Given to women in second or third trimester during influenza season, or if high risk give in first trimester; no confirmed risk to fetus.
Hemophilus influenza type b (HbCV) bacterial polysaccharide, conjugated	Dose for adults has not been determined; generally, one 0.5-ml IM dose is used.	Adults at highest theoretic risk; functional or anatomic asplenia; Hodgkin's disease; consider for HIV-infected persons.	Local erythema and pain; malaise; fever.	Hypersensitivity reaction to conjugated-protein carriers.	Use if indicated; no reported risk to fetus.
Meningococcal bacterial polysaccharide (serogroups A,C, W135, and Y)	One 0.5-ml SC dose; consider revaccination at 3 to 5 years.	Adults with functional or anatomic asplenia or with terminal complement component deficiency; prophylaxis during outbreaks if serogroup represented in vaccine; travelers to endemic areas; consider for college students living in dormatories.	Local erythema and pain.	Severe reaction to previous dose.	Use if indicated; no reported risk to fetus.
Lyme recombinant DNA–derived lipoprotein	Three 0.5-ml IM doses given at 0, 1, and 12 months.	Adults who live and work in wooded or grassy areas that harbor Lyme-bearing ticks.	Local pain and erythema; low-grade fever; arthralgias.	Anaphylaxis to yeast, kanamycin, or previous dose.	Register with manufacturer; unknown risk to fetus.
Rabies human diploid cell (HDCV), rabies vaccine adsorbed (RVA), chick embryo cell culture (PCEC); inactivated virus	Preexposure prophylaxis: 1.0-ml IM doses on days 0, 7, and 28; or 0.1-ml ID doses (HDCV only) on days 0, 7, and 21 or 28; booster dose or antibody titers every 2 years.	Veterinarians, animal handlers, certain laboratory workers, spelunkers, travelers for longer than 1 month to countries where rabies is endemic in domesticated and wild animals.	Local erythema and pain (in 75%), malaise; fever; headache; abdominal pain; myalgias; dizziness (5%-40%); anaphylaxis (0.1%); mild immune complex hypersensitivity re-action in persons given HDCV booster (6%).	Severe reaction to previous dose. Consult public health department if postexposure prophylaxis is needed.	Use if indicated; unknown risk to fetus.
	Postexposure prophylaxis: wound care, then (1) if received appropriate preexposure prophylaxis or previous postexposure prophylaxis, two 1.0-ml IM doses on days 0 and 3; or (2) all other persons, HRIG (20 IU/kg) up to half dose to infiltrate wound and remaining dose IM, with five 1.0-ml IM vaccine doses on days 0, 3, 7, 14, and 28.	Any significant exposure.
Polio inactivated virus (IPV)	IPV preferred for primary vaccination; two 0.5-ml SC doses 1-2 months apart; third dose 6-12 months after second; one booster dose for previously immunized travelers. For accelerated schedule see text.	Travelers to high-risk countries, health care workers exposed to virus.	Rarely, poliomyelitis (OPV); local pain and erythema; rarely, fever (IPV).	Anaphylactic reaction to previous dose, to neomycin or streptomycin (and for IPV, polymixin B). Household contacts and nursing personnel of immunocompromised persons should be given IPV, not OPV.	Use if high risk of infection, no confirmed risk to fetus.
Typhoid live bacteria (oral), inactivated whole bacteria (SC), bacterial polysaccharide (IM)	Four oral doses on days 0, 2, 4, and 6 with series repeated every 5 years; or two 0.5-ml SC doses 4 weeks apart or three SC doses weekly with booster every 3 years; or one 1.0-ml IM dose with a booster every 2 years.	Certain travelers to high-risk areas, certain laboratory workers, household contacts of chronic carrier	Live: nausea, abdominal discomfort, rash; inactivated: local pain and erythema; rarely, fever, malaise, headache.	Severe reaction to previous dose.	Use parenteral form if high risk of infection; no confirmed risk to fetus.
Yellow fever live virus	One 0.5-ml SC dose 10 days to 10 years before travel; booster dose every 10 years.	Certain travelers to areas where yellow fever is endemic.	Low-grade fever; headache; myalgias (2%-5%); extremely rarely, encephalitis.	Severe reaction to previous dose; anaphylaxis to chicken eggs.	Postponement of travel is preferable. Vaccinate if at high risk; attempt waiver if at low risk; unknown risk to fetus.
Japanese encephalitis inactivated virus	Three 0.5-ml SC doses on days 0, 7, and 30; need for booster doses unknown.	Certain travelers to areas where Japanese encephalitis is endemic.	Local erythema and pain; fever; malaise nausea; abdominal discomfort: anaphylaxis precautions.	Severe reaction to a previous dose. Persons with atopy are at risk of severe reactions.	Weigh risk vs benefit; unknown risk to fetus.
Cholera inactivated bacteria	Two 0.5-ml IM or SC doses; or two 0.2-ml ID doses given 1 to 4 weeks apart; booster dose every 6 months.	Travelers to areas that require vaccination or certain travelers at high risk.	Local erythema and pain; fever; malaise.	Severe reaction to previous dose.	Use if high risk of infection; unknown risk to fetus.
IM, Intramuscular; SC, subcutaneous
ID, intradermal; TIG, tetanus immune globulin;HIV, human immunodeficiency virus; HRIG, human rabies immune globulin.

✢See text and Table 5-3 for recommendations and contraindications regarding persons with HIV, severe immunocompromise, or special medical conditions. See Travel and Table 5-7 for more specific travel recommendations.

†If able, it is prudent to wait to vaccinate until after first trimester to minimize concern about teratogenicity. As a contraindication, “pregnancy” also includes the time 3 months (1 month for varicella vaccine) before conception. Breast-feeding is not a contraindication to any vaccine, but more information is available about some vaccines than others (see text).

Intramuscular preparations of IG can be associated with minor reactions (e.g., headache, chills, flushing, nausea) and a pyogenic reaction with high fever. Rarely a hypersensitivity reaction can occur, most often in people with immunoglobulin A (IgA) deficiency. None of the IG preparations has been associated with the transmission of hepatitis B or human immunodeficiency virus (HIV). One product was associated with hepatitis C transmission, but the manufacturing process has been changed.

The Vaccine Adverse Event Reporting System (VAERS) monitors serious adverse reactions to immunobiologics (see Box 5-1). The reported information helps both to improve the general knowledge about adverse reactions, since these reactions are indeed rare, and to provide a database for reactions to newer vaccines. VAERS is also used to stimulate research to confirm a causal association and to identify risk factors for adverse events. Any unusual or severe reaction should be reported to VAERS.

[edit] GENERAL RECOMMENDATIONS

To reduce the morbidity and mortality of vaccine-preventable illnesses, vaccination surveillance should continue throughout adolescence and adulthood and should be part of every routine and episodic visit. The ACIP specifically recommends a systematic immunization review at age 50 to improve immunization rates in adults. To ensure patients' optimal protection against vaccine-preventable illnesses, physicians must learn to evaluate patients according to age criteria and individual risks for specific illnesses. These risks include concomitant medical illnesses, lifestyle, occupational and environmental exposures, ethnicity, and travel plans. Foreign-born persons need to be evaluated for vaccines that they may not have received in childhood (Table 5-2).

All adults should have received a primary tetanus and diphtheria toxoid series (Td) and should be given a booster every 10 years starting in adolescence. Some authorities recommend a single booster at age 50. If the primary series status is unknown, it should be given.

Adults born before 1957 can be considered immune to measles and mumps. In this age group, women of childbearing potential should be tested for rubella antibody and should be vaccinated if not immune. Persons born after 1956 should have been given one dose of measles, mumps, and rubella (MMR) vaccine in childhood at or after 12 months of age or should have laboratory evidence of immunity to all three components of the vaccine. For measles and mumps but not rubella, a physician-diagnosed case may also serve as evidence for immunity.

All adults should be immune to varicella. This can be documented by a reported illness or laboratory immunity. If neither is present, the vaccine should be given.

Adults who are 65 years or older should receive a single dose of pneumococcal vaccine and a yearly influenza vaccine. Their caregivers and household and close family members should be given influenza vaccine as well.

[edit] SPECIAL RECOMMENDATIONS

Certain vaccines may be recommended for persons with particular medical conditions, living situations, or lifestyles. Other vaccines are to be avoided.

[edit] Pregnancy and Breast-feeding

Since many young women receive care in obstetrics and gynecology or family-planning practices, health care providers in these settings should be well versed in vaccination principles and strategies. As part of ongoing preventive health, all women should be evaluated for their risk of vaccine-preventable illnesses and updated on their immunizations.

In addition to any other vaccines that are indicated, women of childbearing age in particular should be current for measles, rubella, and varicella vaccination recommendations because these infections can result in morbidity and mortality in the fetus and newborn. Pregnant women should be tested for hepatitis B infection, and if they are infected, the newborn and household and sexual contacts should be evaluated and treated appropriately. The influenza vaccine should be given to pregnant women who will be beyond their first trimester during the influenza season because of the higher risk for hospitalization. In addition, pregnant women who have medical conditions that increase their risk of complications of influenza should be vaccinated regardless of the stage of pregnancy.

Certain inactivated viral or bacterial vaccines and toxoids are thought to be safe during pregnancy, but some are better studied than others (see Table 5-2). It is prudent to wait until the second trimester to reduce the theoretic risk of teratogenicity. Vaccination should not be delayed, however, if developing the vaccine-preventable illnesses is a risk during the first trimester. Live vaccines should not be given to a pregnant woman or a woman planning to become pregnant within 3 months (1 month for varicella). Household contacts of pregnant women can receive live vaccines. The inadvertent MMR to a pregnant woman has not been associated as yet with congenital rubella syndrome, but the risk of spontaneous abortion is increased in the first trimester. (See sections on individual vaccines for administering the live vaccines yellow fever and oral typhoid during pregnancy.) There is no known risk to the fetus from passive immunization with any IG preparation; they are safe to give in pregnancy and should be used as indicated.

A pregnant woman who needs a varicella, measles, mumps, or rubella vaccination should receive these vaccines immediately after delivery, even if she has received anti-Rh₀ IG or any IG-containing products, so that the opportunity for vaccination is not lost. In this instance, serologic testing should be performed to ensure adequate immune response or the vaccination repeated at the appropriate time interval (see Multiple Vaccines and Immune Globulins).

Inactivated vaccines pose no special risk to breast-feeding mothers or their infants. Live vaccines multiply in the body, but most are not excreted in breast milk. Although rubella can be excreted in the breast milk, it causes only an asymptomatic infection. No data are available for the varicella vaccine, but it is believed to be safe. Giving yellow fever vaccine or oral typhoid vaccine is not contraindicated in breast-feeding women.

[edit] Immunocompromise and Other High-Risk Medical Conditions

Immunocompromise may be the result of infection with HIV, hematologic or generalized malignancies, chemotherapeutic or immunosuppressive agents, radiation, steroids, functional or anatomic asplenia, and complement or immunoglobulin deficiencies. Certain medical conditions are associated with defects in host defense and therefore with a higher incidence of illness or with increased morbidity and mortality from illness because of poor physiologic reserve. The degree of immunocompromise can vary with stage of disease and treatment and should be determined on an individual basis.

Immunizations should be given early in the course of the disease to optimize the immune response. In general, patients can be divided into those with HIV, those with severe immunocompromise not resulting from HIV, and those whose illness does not dictate the avoidance of any vaccine but does necessitate additional vaccines not given to healthy adults. Table 5-3 lists the vaccines recommended for these individuals as well as contraindicated vaccines.

Table 5-3 Recommendations for Persons with Medical Conditions Requiring Special Vaccination Considerations

Condition	Td	MMR	Varicella	HBV	HAV	Pneumovax§	Influenza∥	HbCV	Meningococcal	IPV	Other live vaccines#	Other killed vaccines✢✢
HIV infection	Rou	Rou/Contr✢	Contr†	Rou‡	Rou	Rec	Rec	Cons	Rou	Rou	Contr	Rou
Severe immunocompromise§§	Rou	Contr	Contr†	Rou‡	Rou	Rec	Rec	Rou∥∥	Rou	Rou	Contr	Rou
Renal failure	Rou	Rou	Rou	Rec‡	Rou	Rec	Rec	Rou	Rou	Rou	Rou	Rou
Diabetes	Rou	Rou	Rou	Rou	Rou	Rec	Rec	Rou	Rou	Rou	Rou	Rou
Chronic liver disease	Rou	Rou	Rou	Rou	Rec	Rec	Rec	Rou	Rou	Rou	Rou	Rou
Cardiac disease	Rou	Rou	Rou	Rou	Rou	Rec	Rec	Rou	Rou	Rou	Rou	Rou
Pulmonary disease	Rou	Rou	Rou	Rou	Rou	Rec	Rec	Rou	Rou	Rou	Rou	Rou
Alcoholism	Rou	Rou	Rou	Rou	Rou	Rec	Rec	Rou	Rou	Rou	Rou	Rou
Functional/anatomic asplenia	Rou	Rou	Rou	Rou	Rou	Rec##	Rec	Rec##	Rec##	Rou	Rou	Rou
Terminal complement deficiency	Rou	Rou	Rou	Rou	Rou	Rou	Rou	Rou	Rec	Rou	Rou
Clotting factor disorders	Rou	Rou	Rou	Rec	Rec	Rou	Rou	Rou	Rou	Rou	Rou	Rou
Rou, Routine as outlined for all adults; Contr, contraindicated; Rec, recommended; Cons, consider vaccination; see Box 5-1 for vaccine abbreviations.

✢For asymtomatic, nonseverely immunocompromised persons with human immunodeficiency virus (HIV), MMR can be used; it is contraindicated in severely immunocompromised persons. MMR can be considered in symptomatic HIV patients without severe immunocompromise.

†Varicella can be given to household members and caregivers, but if varicella-like rash develops after vaccination, contact should be avoided.

‡Recommended for persons with severe chronic renal failure approaching or already receiving dialysis, and higher doses should be given. Antibody titers should be measured after vaccination in these patients and in those with HIV or severe immunocompromise (who may require higher doses) to ensure adequate response. Yearly titers should be measured in dialysis patients.

§Pneumovax should be repeated in 5 years for patients in whom vaccine is recommended. Asthma without chronic obstructive pulmonary disease is not an indication for the vaccine.

∥Influenza vaccine should also be given to caregivers and household members.

1. Includes bacille Calmette-Guérin, vaccinia, oral typhoid, yellow fever (if exposure cannot be avoided, persons with HIV can be given yellow fever vaccine; see text).

✢✢Includes rabies (check postvaccination titers in HIV or severely immunocompromised persons), Lyme, inactivated typhoid, cholera, plague, and anthrax.

§§Severe immunocompromise can result from congenital immunodeficiency, leukemia, lymphoma, malignancy, organ transplant, chemotherapy, radiation therapy, or high-dose corticosteroids.

∥∥Only for persons with Hodgkin's disease.

1. 1. Give at least 2 weeks in advance of elective splenectomy.

[edit] Human Immunodeficiency Virus Infection.

Persons with HIV should be evaluated for their vaccination history and their risk of vaccine-preventable illnesses, as outlined for all adults. In addition, certain vaccines are especially recommended because of increased disease susceptibility or severity.

Inactivated viral or bacterial vaccines and toxoids can be given to HIV patients. In general, HIV-infected individuals should not be given live virus vaccines because of the risk of uncontrolled viral replication. If indicated, however, an MMR is recommended for those with asymptomatic HIV infection without evidence of severe immunosuppression because of a high risk of exposure to measles. Measles infection in these patients can be serious, and in limited studies the vaccine has been safe. For symptomatic patients without evidence of severe immunosuppression, the vaccine should be considered in high-risk situations. The vaccine is contraindicated for those with severe immunosuppression because of poor efficacy. Measles pneumonitis has occurred in a severely immunosuppressed HIV patient, and vaccine-induced morbidity has occurred in other immunocompromised patients.

Any needed immunization should be given early in the course of the disease rather than later, when the immune response may be suboptimal. The efficacy of vaccines in this group of patients has not been studied. In theory, people who do not respond adequately to initial vaccination may respond to higher doses of vaccine or to additional doses, but this also has not been evaluated.

[edit] Severe Immunocompromise Without HIV Infection.

Individuals can be severely immunocompromised as a result of hematologic or general malignancy, chemotherapy, radiation therapy, high doses of corticosteroids (generally the equivalent of 20 mg/day prednisone for longer than 2 weeks), or other immunosuppressive therapies. The degree of immunocompromise should be evaluated on an individual basis. Steroids given for less than 2 weeks; alternate-day therapy with short-acting, low-dose preparations; physiologic replacement doses; topical preparations used for either skin, eye, or lung; or injections into joints are not considered immunosuppressive for the purpose of vaccination decisions. Vaccines should be given early in the course of a disease rather than later, when the immune response may be suboptimal.

Ideally any vaccination should precede chemotherapy or radiation therapy by more than 2 weeks and should be avoided during chemotherapy because of a potential suboptimal response. A vaccine should be given at least 3 months after chemotherapy; however, the ability to mount an immune response may be compromised for up to a year. For patients receiving high-dose corticosteroids for more than 2 weeks, vaccines should be given 3 months after discontinuation of the drug. If the duration of the high-dose corticosteroid use is less than 2 weeks, waiting 2 weeks may suffice. If the strength of a patient's immune response is in doubt, antibody titers may be helpful, or the vaccination can be repeated.

Individuals with severe immunocompromise should be evaluated for their vaccination history and their risk of vaccine-preventable illnesses, as outlined for all adults. In addition, certain vaccines are recommended especially for them.

Inactivated viral or bacterial vaccines and toxoids are safe for all severely immunocompromised patients. Live vaccines are contraindicated unless the immunocompromise is reversible (steroids, chemotherapy, radiation therapy, or other immunosuppressive therapy) and an appropriate interval has elapsed between discontinuation of therapy and administration of live vaccine.

[edit] Lifestyle and Environmental Risk

Homosexual and bisexual men and injection drug users are at increased risk for hepatitis A and B infection; 35% to 80% have serologic evidence of hepatitis B exposure. They should be screened for hepatitis A and B exposure; if not already immune or infected, they should be vaccinated. People should be evaluated early because continued exposure increases the chance of infection; 10% to 20% of homosexual men are infected with hepatitis B each year. Hepatitis B vaccine is also recommended for prostitutes, heterosexuals with multiple sex partners, and individuals with sexually transmitted diseases (STDs). Persons in these risk groups should be evaluated for hepatitis C, HIV, and other STDs because of concomitant risk. Injection drug users have an increased incidence of tetanus; physicians should be diligent in giving a Td to these patients.

Inmates of long-term correctional facilities have a high prevalence of hepatitis B, ranging from 10% to 80%, largely because of injection drug use and male homosexual activity. They should be screened for hepatitis B exposure and associated diseases. In addition, measles and rubella outbreaks have occurred in these facilities, and all inmates should be evaluated for immunity or vaccinated as appropriate if at increased risk.

The prevalence of hepatitis B in large institutions for developmentally disabled patients is 35% to 80%. Residents should be screened for hepatitis B exposure; if not already immune or infected, they should be vaccinated. Newly admitted persons should be vaccinated for hepatitis B. All residents should be given a yearly influenza vaccine because some residents may have medical illnesses that make influenza more serious. The staff should also be given hepatitis B and influenza vaccines.

Homeless persons are at risk for pneumococcal disease and influenza and should be vaccinated. Shelter staff should also be given influenza vaccine. There is a high prevalence of hepatitis B in the Native Alaskan population. These individuals should be screened for hepatitis B exposure; if not already immune or infected, they should be vaccinated. Also, Native Alaskan and some Native American populations are at increased risk for invasive pneumococcal disease and should be vaccinated.

[edit] Occupational Risk

Health care workers not only are at increased risk of exposure to illness but also can transmit the illness to susceptible patients.

Health care workers born after 1956 should either (1) have been vaccinated twice for measles and once for mumps and rubella after their first birthday, (2) have had physician-diagnosed measles and mumps, or (3) have laboratory immunity to all three diseases. In addition, health care facilities should consider requiring one dose of measles vaccine for employees born before 1957 unless they have serologic proof of measles immunity or have had physician-diagnosed measles. A significant number of cases of measles are reported in health care workers born before 1957.

Although all adults are recommended to have immunity to varicella, this is especially important in health care workers, and verified through reported illness, laboratory immunity, or vaccination. The employee who develops a varicella-like rash after immunization should avoid patient exposure until the lesions crust over. All health care workers and support staff who have patient contact should also be given a yearly influenza vaccine.

People with direct patient contact and laboratory personnel working with blood or body fluids should be immunized against hepatitis B. Individuals with frequent exposure to blood in this setting have a 15% to 30% prevalence of hepatitis B infection, compared with less than 5% in the general population. An antibody titer should be measured after the vaccine series because it is useful in determining postexposure prophylaxis.

Bacille Calmette-Guérin (BCG) vaccine is recommended for health care workers exposed to multidrug-resistant tuberculosis when other efforts to decrease transmission have failed.

Hepatitis B vaccine is recommended for public safety personnel (e.g., police, firefighters, emergency medical technicians) who may be exposed to blood and secretions. It is also recommended for the staff of institutions for developmentally disabled persons because of the high prevalence of hepatitis B in the patients and the risk of exposure through bites or contact with blood, saliva, skin lesions, or other infectious secretions. These staff workers should also be given a yearly influenza vaccine.

Preexposure rabies vaccine should be given to laboratory workers who handle the virus, to veterinarians, and to animal handlers and field personnel who work with dogs, cats, raccoons, bats, and skunks. Those with avocations that bring them into contact with potentially rabid animals should also be considered for immunization. Preexposure vaccination eliminates the need for postexposure human rabies IG and reduces the number of rabies vaccines needed.

Laboratory personnel who may handle specimens containing poliovirus, smallpox or other orthopoxviruses, hepatitis A virus, Yersinia pestis, or Bacillus anthracis should be vaccinated for these illnesses. Anyone working with imported hides, furs, wools, and animal hair should receive anthrax vaccine. Field personnel dealing with rodents, rabbits, or their fleas should receive plague vaccine.

[edit] Students

Students in colleges, universities, or other postgraduate institutions should be evaluated on entry for any needed vaccination, as outlined for adults. Foreign students should provide documentation of prior vaccination or should be considered unvaccinated. Because of measles epidemics in universities, students born after 1956 should have been given two doses of measles vaccine after their first birthday, have had physician-diagnosed measles, or have serologic evidence of immunity. Meningococcal vaccine can be considered for college students living in dormitories. Students entering the health care profession also should be evaluated as for health care workers.

[edit] Immigrants and Refugees

In many countries, routine vaccines are not given. Foreigners entering the United States should provide documentation or receive vaccinations appropriate to their age and concomitant risk. For some vaccines, this may require a primary series. People from areas endemic for hepatitis B (see Table 5-7) should be screened for the virus; if they are carriers, susceptible household members and sexual partners should be evaluated. Individuals from countries with endemic hepatitis B who reside in a similar cultural community in the United States should be given hepatitis B vaccine if they are not already immune or infected.

Table 5-7 Recommendations for Travelers

Modified from CDC: Immunization of health care workers: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HICPAC), MMWR 46(RR-18):23, 1997.

Disease✢	Areas affected†	Prophylaxis recommended‡	Ideal time between last vaccine dose and travel
Tetanus	All	All travelers; vaccine series/booster.	Probably 30 days for series Anamnestic response to booster
Measles	All	Born after 1956; ensure immunity by antibody titer, diagnosed measles, or two doses of vaccine.	As MMR, 7-14 days
Rubella	All	Born after 1956 and any female of childbearing age; rubella titer or one dose of vaccine.	As MMR, 7-14 days
Mumps	All	Born after 1956; ensure immunity by antibody titer, diagnosed mumps, or one dose of vaccine.	As MMR, 7-14 days
Varicella	All	All travelers; antibody titer, reported illness, or vaccine series.	7-14 days
Hepatitis B	5%-20% of population are carriers in Africa, Middle East except Israel, all Southeast Asia, Amazon basin, Haiti, and Dominican Republic; 1%-5% of population are carriers in south-central and southwest Asia, Israel, Japan, Americas, Russia, and eastern and southern Europe.	Travelers for more than 6 months in close contact with population or for less time but with high-risk activities (close household contact, seeking dental or medical care, sex); vaccine series.	Probably 30 days
Hepatitis A	Developing countries.	Travelers to rural areas; eating and drinking in settings of poor sanitation; vaccine or pooled immune globulin (IG).	Vaccine, 30 days Pooled IG, 2 days
Influenza	Tropics throughout the year; southern hemisphere from April to September.	Travelers for whom vaccine is otherwise indicated; give current vaccine and revaccinate in fall as usual.	7-14 days
Meningococcus✢	Sub-Saharan Africa “belt” (Senegal to Ethiopia) from December to June; required for pilgrims to Saudi Arabia during Haj; epidemics reported in other African nations, India, Nepal, and Mongolia.	All travelers; vaccine.	7-10 days
Rabies	Endemic dog rabies exists in Mexico, El Salvador, Guatemala, Peru, Columbia, Ecuador, India, Nepal, Phillipines, Sri Lanka, Thailand, and Vietnam.	Travelers staying for more than 30 days or at high risk of exposure to domestic or wild animals; vaccine series/booster.	7-14 days
Poliomyelitis	Developing countries not in western hemisphere; at risk all year in tropics; in temperate zones, incidence increases in summer and fall.	All travelers; vaccine series/booster.	Parenteral vaccine series, 28 days (see text) Anamnestic response to booster
Typhoid fever	Many countries in Asia, Africa, Central America, and South America.	Travelers with prolonged stay in rural areas with poor sanitation; vaccine series/booster.	Oral vaccine, 7 days Parenteral vaccine, probably 14 days
Yellow fever✢	North and central South America, forest-savannah zones of Africa; some countries in Africa, Asia, and Middle East require travelers from endemic areas to be vaccinated.	All travelers; vaccine/booster at approved yellow fever vaccination center.	10 days
Japanese encephalitis	Seasonally in most areas of Asia, Indian subcontinent, and western Pacific islands; in temperate zones, incidence increases in summer and early fall; in tropics, year-round incidence.	Travelers staying for more than 30 days in high-risk rural areas; staying outdoors during transmission season; vaccine series.	10 days
Cholera✢	Certain undeveloped countries.	If required by local authorities, one dose usually suffices; primary series only for those living in high-risk areas under poor sanitary conditions or those with compromised gastric defense mechanisms (achlorhydria, antacid therapy, previous ulcer surgery); booster every 6 months.	Probably 30 days
Plague	Africa, Asia, and Americas in rural mountainous or upland areas.	Travelers whose research or field activities bring them in contact with rodents; vaccine series/booster; consider taking tetracycline (500 mg four times a day) for chemoprophylaxis (inferred from clinical experience in treating plague).	Probably 30 days

✢Only yellow fever vaccine is required for entry by any country; cholera vaccine may be required by some local authorities; and meningococcus vaccine is required for pilgrims to Mecca, Saudia Arabia, during Haj. However, it is important to follow CDC recommendations for all vaccines to prevent disease. If a required vaccine is contraindicated or withheld for any reason, attempts should be made to obtain a waiver from the country's consulate or embassy.

†Because areas affected can change, and for more specific details, consult CDC's traveler's hotline (see Box 5-1).

‡For detailed information concerning administration of individual vaccines, see text under each vaccine and Table 5-2.

[edit] VACCINE-PREVENTABLE ILLNESSES, VACCINES, AND POSTEXPOSURE PROPHYLAXIS

The following sections discuss vaccines individually. Table 5-2 summarizes vaccines, dose schedules, indications, contraindications, and side effects.

[edit] Tetanus and Diphtheria

Tetanus vaccine became available in the United States in the middle-to-late 1940s. Its use has contributed to a 90% reduction in the incidence of tetanus morbidity and mortality. The shift in population from rural to urban areas (resulting in a decreased exposure to spores), improved wound care, and postexposure prophylaxis have also contributed to this phenomenon. Vaccination of school-age children is required in 47 states, and since 1980 more than 95% of students have received a primary series.

Vaccination of adults is much more sporadic. Between 31% and 71% of older adults lack antibody to tetanus. Of the 50 to 100 cases of tetanus in the United States reported annually, 94% occur in adults over 20 years old and 70% in adults 50 years or older. Many of these individuals were born outside the United States and never had a primary immunization series. Of those with a known vaccination history, 93% have not received a primary series or booster dose. The case fatality rate is approximately 25% and increases with age; all recently reported deaths have occurred in adults older than 40 years.

Most individuals with reported tetanus have an identifiable acute injury: puncture, laceration, abrasion, bite, or scratch. Other sources of entry include chronic ulceration, abscess, or history of injection drug use. Only one third of those with tetanus sought medical care after an injury; of these, 75% were not appropriately managed according to current recommendations. The incubation period for clinical disease in most cases is 3 days to 3 weeks, with an average of 8 days.

Diphtheria is rare in the United States. Until recently, an average of only two cases per year have been reported, the majority in persons older than 20 years. Between 40% and 80% of adults older than 60 years lack protective antibody.

Td, a combined preparation of adsorbed tetanus toxoid derived from the bacterium Clostridium tetani and diphtheria toxoid derived from Corynebacterium diphtheriae, is recommended for adults. It contains tetanus toxoid and 25% less diphtheria toxoid than the childhood immunization to reduce side effects (the childhood vaccine is denoted DT). The vaccine is almost 100% effective in preventing tetanus and 85% effective in preventing diphtheria. The vaccine does not contain any pertussis immunogens because the current whole-cell preparation has an unacceptably high frequency of side effects. An acellular preparation of Bordetella pertussis is being studied in adults in an effort to decrease the spread of the disease by asymptomatic adult carriers.

People who develop urticaria or anaphylaxis to the vaccine should be tested for allergy before further doses are restricted. If an acute exposure occurs in these individuals, tetanus immune globulin (TIG) should be given.

Table 5-4 summarizes the management of postexposure prophylaxis for tetanus. Immune prophylaxis should be administered as soon as possible, ideally within 3 days, but can be given later if delay is unavoidable. Local wound care is important. The need for a Td and TIG depends on the patient's vaccination status and the type of injury sustained. The physician must determine exactly how many doses of vaccine the patient received in the past. In particular, immigrants, refugees, and foreign students should be evaluated to ensure that they received the primary series (often not routinely given during childhood in other countries). If receipt of a full primary series is uncertain, the patient should be managed as if unvaccinated. If a person has had a primary series, evaluating the date of the last dose given is important. If a Td is indicated after an exposure but is contraindicated because of a previous severe reaction, TIG should be given instead. If TIG (250 U intramuscularly) is to be given with a Td, separate sites should be used. Arrangements should be made to have patients complete a primary series if they have not done so previously. If TIG is given, ideally an MMR vaccine should not be given until 3 months later and varicella vaccine not until 5 months later.

Table 5-4 Postexposure Immunoprophylaxis for Tetanus

Modified and updated from CDC: Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence, MMWR 42(RR-4):16 and 17, 1993.

Tetanus vaccine doses	Clean, minor wounds		All other wounds✢
		Td	TIG	Td	TIG
Uncertain or less than three†	Yes	No	Yes	Yes
Three or more‡	No§	No	No∥	No
Td, Adsorbed tetanus and diphtheria toxoid for adult use (0.5 ml intramuscularly) as soon as possible and preferably within 3 days.
TIG, Tetanus immune globulin (250 U intramuscularly) as soon as possible and preferably within 3 days.

✢Including but not limited to wounds contaminated with dirt, feces, soil, or saliva, as well as puncture wounds, avulsions, or wounds resulting from missiles, crushing, burns, or frostbite.

†Follow-up arrangements should be made to complete primary series.

‡If only three doses of a fluid toxoid have been received (used in some countries but less effective), a fourth dose of adsorbed tetanus toxoid should be given regardless of type of wound.

§Yes, if more than 10 years since last dose.

∥Yes, if more than 5 years since last dose.

[edit] Measles, Mumps, and Rubella

The U.S. Public Health Service has called for the elimination of measles, rubella, and congenital rubella by the year 2000 and has established initiatives for widespread vaccination to accomplish this goal.

[edit] Measles.

Measles vaccine became available in the United States in 1963, and subsequently the cases of measles declined by 99%, to a low of 3600 in 1988. In 1989 and 1990, however, outbreaks of measles occurred, and the reported cases rose to 28,000. Two major types of outbreaks were noted: (1) among unvaccinated school-age children, including those younger than the recommended age for vaccination (less than 12 months), and (2) among vaccinated school-age children. Also, in 1989 a substantial number of cases occurred among students and personnel on college campuses. In response to these outbreaks, it was recommended in 1990 that all children receive two doses of measles vaccine. Two doses were also recommended for adolescents, adults born after 1956, and high-risk groups. Subsequently the number of measles cases declined to 508 in 1996, of which 65 were imported. Only 100 cases were reported in 1998. A similar two-dose regimen used in Finland for more than 12 years has virtually eliminated the disease in that country.

Persons born before 1957 are generally considered immune, although serologic testing of hospital workers in 1989 and 1990 revealed that up to 9% born before 1957 were not immune. Of the health care workers who developed measles during 1985 to 1990, 29% were born before 1957. Encephalitis or death from measles occurs in one per 1000 cases.

Measles infection during pregnancy can result in spontaneous abortion, premature labor, and low birth weight. Although malformations have been reported in association with measles infection, no specific syndrome has been described.

[edit] Mumps.

Live mumps vaccine was available in 1967, but because of cost, it was not routinely used until 1977. The number of reported cases of mumps declined from 185,000 in 1968 to 2000 in 1985 but rose in 1987 to 12,000 because of an unvaccinated cohort of young adults. The number of cases has been declining since then, and 666 cases were reported in 1998. Mumps is generally a self-limiting illness. Although orchitis can occur in postpubertal males, sterility is rare.

[edit] Rubella.

The live rubella vaccine was licensed in the United States in 1969. The incidence of rubella infection declined from 56,000 cases in 1969 to 225 in 1988 but rose to 930 cases in 1990, with outbreaks in prisons and colleges. An estimated 6% to 11% of adolescents and young adults are susceptible to rubella. Of the cases reported in 1992 to 1997, averaging 200 to 300, more than 65% were in young adults.

The goal of vaccination is to prevent fetal infection and congenital rubella syndrome (CRS). Of infants infected during the first trimester, 25% will develop CRS that is recognizable at birth, and another 55% will have milder debilitating defects. Defects are rare when infections occur after 20 weeks' gestation. Pooled IG given as postexposure prophylaxis has no proven benefit in preventing fetal malformations.

[edit] Vaccine.

When a measles, mumps, or rubella vaccine is indicated, the live trivalent vaccine (MMR), which contains all three immunogens, should be used because it provides additional protection against two other diseases. A single dose of an MMR provides long-lasting immunity in 90% to 95% of recipients, whereas two doses provides 99%. Of note, rubella vaccine grown in human diploid cell cultures rather than chicken embryos is available and safe for those with anaphylactic reactions to chicken eggs who need the rubella vaccine. Because it is a live virus vaccine, certain principles apply to giving an MMR and other live vaccines or IGs (see Multiple Vaccines and Immune Globulins on p. 37) to pregnant or immunocompromised persons (see Special Recommendations on p. 38).

[edit] Prophylaxis.

Postexposure prophylaxis for measles should be given to any susceptible person and any patient with severe immunocompromise or symptomatic HIV regardless of vaccination status. Although no data exist on benefits to the fetus, special consideration should be given for administration of pooled IG to susceptible pregnant women exposed to measles.

The incubation period after exposure is generally 8 to 12 days. People are contagious for 1 to 2 days before the onset of symptoms (3 to 5 days before the rash) and up to 4 days after the appearance of the rash. Measles is transmitted by direct contact with infectious droplets and less often by airborne spread. Susceptible individuals exposed to measles should avoid contact with susceptible health care workers, pregnant women, and patients, as well as severely immunocompromised or symptomatic patients with HIV regardless of vaccination status, for 5 to 21 days after the exposure, even if postexposure prophylaxis is given. People who are ill with measles should avoid such contact for 7 days after they have developed the rash.

Measles illness may be modified in susceptible contacts by giving an MMR within 72 hours of exposure. Giving an MMR has the advantage of providing protection against subsequent measles exposure. If giving an MMR is contraindicated (e.g., pregnancy, symptomatic HIV, severe immunocompromise), or if the person is unlikely to mount an adequate immune response, pooled IG should be given within 6 days of exposure.

The dose of pooled IG for measles exposure in a healthy adult is 0.25 ml/kg (equivalent to 40 mg IG/kg) intramuscularly (IM), to a maximum of 15 ml. Severely immunocompromised patients and symptomatic patients with HIV should receive pooled IG regardless of their vaccination history at twice the dose given to healthy people, or 0.50 ml/kg (equivalent to 80 mg IG/kg) IM, to a maximum of 15 ml. If an immunocompromised patient is receiving a standard dose (100 to 400 mg/kg) of intravenous IG for other reasons at regular intervals, and if the last dose was given within 3 weeks of the measles exposure, this may be sufficient to prevent measles. When pooled IG is indicated and IM injection is contraindicated, as in patients with severe thrombocytopenia or a coagulation disorder (e.g., hemophilia), an intravenous preparation can be used at a dose of 110 mg/kg. Because these intravenous IG preparations are derived from smaller donor pools, they may not be as effective for measles prophylaxis. Their efficacy for these purposes is unknown, and therefore no specific recommendation exists.

If pooled IG is used for measles prophylaxis, an MMR should be given to healthy people after 5 months and to immunocompromised or symptomatic HIV patients after 6 months if it is not contraindicated at that time. If intravenous IG was used, an MMR vaccine should not be given until after 6 months for a 100-mg dose and up to 8 months later for a 400-mg dose. A second MMR may be indicated for those born after 1956 if they are at high risk of subsequent measles exposure.

[edit] Varicella

Varicella is a highly contagious childhood illness, with secondary attack rates in household members of up to 90%. Infection confers lifelong immunity, except in rare cases of reinfection in immunocompromised persons. In adults the disease is more serious than in children and can have associated pneumonitis, bacterial superinfections, encephalitis, hepatitis, and death. The severity is increased in older individuals and severely immunocompromised patients.

Varicella infection in a woman during the first half of pregnancy can result in embryopathy in up to 2% of cases. Varicella infection in women 5 days before and up to 2 days after delivery can result in disease in 30% of newborns, which is often severe.

Up to 15% of adults will develop varicella-zoster infection, which can become disseminated in immunocompromised patients.

In the United States, more than 90% of adults are immune, although the rates are lower for those in tropical or subtropical regions. Of those who report a history of varicella, 97% to 99% have serologic immunity, and of those who report a negative history, 71% to 93% will have antibody. Reported illness or laboratory evidence confers immunity in healthy and immunocompromised persons, except for bone marrow recipients, who are never considered immune, and for immunocompromised persons who received multiple transfusions and who have a negative history with a low varicella titer, because the antibody could have been acquired passively.

The live virus vaccine was licensed in 1995 and is recommended for all children and nonimmune adults, especially persons who live and work in environments where transmission of varicella is likely (i.e., households with children, colleges, prisons, day-care, medical facilities), nonpregnant women of childbearing age, and international travelers. One dose of the vaccine induces a seroconversion rate of 78% to 82%, and a second dose induces 99%. Salicylate ingestion should be avoided for up to 6 weeks after vaccination because of the Reye's syndrome associated with wild varicella. If a varicella-like rash develops after vaccination, contact with all susceptible persons should be avoided, and health care workers should probably be furloughed. In this setting, VZIG is not recommended for susceptible contacts because transmission is rare and disease is expected to be mild.

The vaccine is 70% effective in preventing any disease and 95% effective in preventing serious disease. Persons who develop varicella despite vaccination generally have fewer lesions, shorter illness, and less fever. The vaccine is effective in children for at least 20 years. The need for booster doses is unknown but is continually monitored, especially since the illness in adults is more severe than in children. It is not known whether the vaccine will decrease the incidence of zoster.

Because it is a live virus vaccine, certain principles apply to giving a varicella vaccine and other live vaccines or IGs (see Multiple Vaccines and Immune Globulins on p. 37) to pregnant or immunocompromised persons (see Special Recommendations on p. 38).

A significant exposure to a person with chickenpox includes household contact, close indoor contact longer than an hour, sharing a hospital room, or prolonged face-to-face contact (e.g., physician and patient). The period of highest risk of contagion is 1 to 2 days before the onset of the rash and for 5 days after or until the last eruptions form a crust. Immunocompromised patients may have an extended period of new eruptions and therefore are contagious longer. A significant exposure to a person with shingles results from direct contact with uncovered lesions; airborne spread is rare. An immunocompromised patient with shingles, however, may shed a large viral load that can be aerosolized; in this setting, significant exposure may occur, as described for chickenpox.

Any person with wild or vaccine-associated varicella should avoid contact with susceptible persons for at least 5 days after the onset of the rash and for the duration of any new eruptions or until all the lesions have crusted over, whichever is longer. The incubation period is generally 14 to 16 days but can be anytime from 11 to 20 days. Exposed, susceptible people should avoid other susceptible persons for 10 to 21 days after the development of the rash in the index patient. Those who receive varicella-zoster immune globulin (VZIG) for postexposure prophylaxis should avoid contact with susceptible individuals for 28 days because VZIG may prolong the incubation period of clinical disease.

The decision regarding the administration of postexposure prophylaxis for varicella has been simplified because the vaccine is now approved for this purpose. VZIG can be used for those persons who cannot receive the vaccine: immunocompromised persons or pregnant women. The decision to administer VZIG for postexposure prophylaxis is based on the significance of the exposure as discussed above and the likelihood that an individual is susceptible to varicella. Even if IG aborts clinical disease in a pregnant woman, it is not known whether this protects the infant from infection and malformation.

Susceptibility to the illness needs to be evaluated on an individual basis. Even with negative histories, elder siblings in large families, parents whose children have had chickenpox, or those who have had other significant exposure to chickenpox are probably immune. It is preferable to measure a varicella antibody titer in people with an unknown susceptibility to determine their immune status, if this will not delay the administration of the vaccine beyond 72 hours or VZIG beyond 48 hours (except for specific immunocompromised persons and bone marrow recipients as noted above). In persons who were previously immunized (initial expected positive titer in 99%) who have a negative titer, no VZIG is needed because the disease is expected to be mild. There is currently no recommendation regarding giving the vaccine as these persons may or may not have an anamnestic response.

For postexposure prophylaxis to prevent or modify the disease, the varicella vaccine is 90% effective if given within 3 days. It may still be effective up to 5 days. The second dose of the vaccine should be given in 1 or 2 months to complete the series. The dose of VZIG is 12.5 U/kg to a maximum of 625 U (the ideal dose has not been determined for immunocompromised individuals) given within 48 hours of exposure and preferably not beyond 96 hours. VZIG prophylaxis in this setting may last up to 3 weeks. If clinical disease does not develop and there is a new exposure after this time, another dose should be given. People who receive VZIG and who do not develop clinical disease may develop serologic immunity, but it is not known whether this is protective against future exposures. If VZIG is given, ideally a varicella or MMR vaccine should not be given until 5 months later.

[edit] Hepatitis B

In certain areas of the world (see Table 5-7), hepatitis B is endemic, with the virus predominantly transmitted perinatally and during childhood. In the United States, most affected people acquire hepatitis B infection during late adolescence or young adulthood through body secretions or blood exposure; more than 89% of the cases occur in individuals older than 20 years. The lifetime risk of developing hepatitis B in the United States is less than 5% for the general population. In high-risk groups, such as injection drug users, it can approach 80%. Approximately 300,000 cases of acute hepatitis B infections occur each year in the United States, resulting in 10,000 hospitalizations and 250 deaths. The rate at which persons become chronic carriers is age dependent; infection in adults is associated with a 6% to 10% chronic carrier rate, infection in childhood with a rate as high as 60%, and perinatal infection with a rate as high as 90%.

Each year in the United States, 4000 people die of cirrhosis and 800 people die of liver cancer related to hepatitis B infection. Because Native Alaskans have a high incidence of hepatitis B, they were the subjects of a perinatal and adult vaccination program in 1982. The incidence of acute hepatitis B was reduced by 99%. In some countries with endemic hepatitis B, widespread vaccination has correlated with a reduction in chronic liver disease and hepatocellular carcinoma.

Previously, high-risk groups were targeted for vaccination in an effort to decrease the incidence of disease, but the incidence continued to rise. Since 1990 it has been recommended that all newborns in the United States be given hepatitis B vaccine. The vaccine also is recommended for all adolescents and certain adults in high-risk groups (see Table 5-2) and for certain travelers (see Table 5-7). Travelers to countries where hepatitis B is endemic can minimize exposure by avoiding intimate contact with the native population, especially contact involving blood, sex, and prolonged household contact.

Prevaccination screening for active disease should be done for high-risk groups, such as homosexual men, injection drug users, hemodialysis patients, recipients of multiple infusions of clotting factor concentrates or whole blood, and immigrants from high-risk countries, to identify people who are infected and who may benefit from treatment, as well as their household and sexual contacts who are at risk. Using any one serologic marker for screening is imperfect. Screening for hepatitis B surface antigen (HBsAg) alone would identify those who are currently infected, but not those who are immune and do not require vaccination. Screening for hepatitis B surface antibody (anti-HBs) alone would identify most of those who are immune, but not those who are infected, for whom treatment and evaluation of sexual or household contacts are important.

Screening for hepatitis B core antibody (anti-HBc) alone identifies anyone infected but does not differentiate between carriers and noncarriers. Anti-HBc could be tested if the goal of screening is to eliminate individuals who theoretically do not require vaccination. This is problematic, however, because people who have anti-HBc alone cannot necessarily be considered immune. In a study of United States blood donors with a relatively low incidence of hepatitis B, one quarter of patients who had isolated anti-HBc alone were shown to have a false-positive test. In several studies of populations with endemic hepatitis B, people with anti-HBc alone that was persistent and reproducible had a variable response to vaccination. Less than 20% had an anamnestic response, suggesting that more than 80% were not immune. In addition, 10% to 40% had no response to a full series, suggesting a low-level carrier state. These studies suggest that people with anti-HBc alone and their at-risk contacts should be included in vaccination programs targeting high-risk groups. Therefore, to screen persons from high-risk groups, it is prudent to measure at least HBsAg and anti-HBs.

The vaccines used in the United States today contain purified HBsAg made with recombinant DNA technology. In adults the vaccine series is greater than 90% effective in preventing clinical disease. In some studies the antibody response to vaccination is reduced in older adults and in smokers or obese persons (perhaps a function of inadequate IM injection). If doses are missed in the usual series of 0, 1, and 6 months, the second and third doses should be given at least 2 months apart. A higher dose formulation is available for persons who may have a poor immune response to the standard vaccine (e.g., HIV, severe immunocompromise, approaching or on dialysis).

Postvaccination antibody testing is recommended for anyone at occupational risk to aid in deciding postexposure prophylaxis, as well as for immunocompromised persons and persons with renal failure who may have suboptimal response to the vaccine. Postvaccination titers should be evaluated at least 1 month after the series is completed. In one study of nonresponders to the vaccine series, 15% to 25% developed an adequate antibody titer to one additional dose. An additional 30% to 50% developed an adequate antibody response to another series. Revaccination with one or more doses should be considered for nonresponders after the presence of HBsAg has been excluded.

In healthy individuals, immunologic memory seems to persist for up to 15 years despite antibody titers below the threshold for immunity, as demonstrated by the absence of clinical disease and HBsAg in the serum during this time period. Currently, booster doses are not recommended for healthy individuals, although this may change in the future. Yearly antibody titers should be measured in hemodialysis patients because of the rapid decline in their antibody titers. A booster should be given if the antibody titer falls below 10 U/ml.

Tables 5-5 and 5-6 summarize recommendations for postexposure management of hepatitis B. Sexual and household contacts of a person with chronic hepatitis B should be evaluated for immunity and infection; if they have neither, they should receive hepatitis B vaccine (HBV). Sexual contacts of someone with acute hepatitis B should receive hepatitis B immune globulin (HBIG) as soon as possible and within 2 weeks of the last exposure; this is 75% effective in preventing disease. Contacts can be tested for an already-acquired infection if testing will not delay giving HBIG or HBV more than a few days. If sexual contact is not likely to continue and the exposed person is otherwise at low risk for exposure to hepatitis B in the future, one dose of HBIG is sufficient (adding one dose of HBV may increase effectiveness). HBIG should be given with HBV and the series of HBV completed if sexual contact is likely to continue. Alternatively, HBIG can be given (adding one dose of HBV may increase effectiveness) and the index person retested in 3 months. If the index person is not still infectious, nothing further is needed. If the index person is still infectious, a second HBIG should be given and the HBV series started in the partner. Household contacts of someone with acute hepatitis B who have a known exposure, such as blood contact through toothbrushes or razors, should be treated similarly to those with sexual exposure.

Table 5-5 Postexposure Immunoprophylaxis for Hepatitis B Virus in Susceptible Contacts After Sexual or Household Exposure

Modified from CDC: Update on adult immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP), MMWR 40(RR-12):70, 1991.

Index person	Exposure type	Immunoprophylaxis
Chronically infected	Household or sexual	Vaccination series
Acutely infected	Household with no blood exposure	None unless blood exposure
Acutely infected	Sexual or house-hold with blood exposure	HBIG with or without vaccination series✢
HBIG, Hepatitis B immune globulin (0.06 ml/kg intramuscularly) as soon as possible and within 2 weeks of last sexual or household exposure.
Hepatitis B vaccine (1.0 ml intramuscularly) as soon as possible and within 2 weeks of last exposure to acutely infected person and as soon as possible after exposure to chronically infected person.

✢See text.

Table 5-6 Immunoprophylaxis for Hepatitis B Virus After Percutaneous or Permucosal Exposure to Blood

Modified from CDC: Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: recommendations of the Immunization Practices Advisory Committee (ACIP), MMWR 40(RR-13):9, 1991.

Exposed person	Treatment, when source is:
		HBsAg positive	HBsAg negative	Unknown
Unvaccinated	HBIG and vaccine series✢	Vaccine series✢	Vaccine series✢
Previously vaccinated
Known responder	None	None	None
Known nonresponder	HBIG at 0 and 1 month, or HBIG and vaccine series✢	None	If high-risk source, treat as HBsAg positive
Response unknown	Test exposed person for anti-HBs titer:	Test exposed person for anti-HBs titer for future exposure management	Test exposed person for anti-HBs titer:
	1. If adequate, none		1. If adequate, none
	2. If inadequate, HBIG and vaccine series✢		2. If inadequate, vaccine series✢
HBsAg, Hepatitis B surface antigen; anti-HBs, Hepatatitis B surface antibody; adequate anti-HBs titer >10 mIU.
HBIG, Hepatitis B immune globulin (0.06 ml/kg intramuscularly) as soon as possible and within 24 hours of exposure. Unclear efficacy if given after 1 week of exposure.
Hepatitis B vaccine (1.0 ml intramuscularly) as soon as possible and within 1 week of exposure.

✢Check for antibody titer at least 1 month after series to guide management of future exposures.

Table 5-6 summarizes the management of percutaneous (needle-stick, laceration, or bite) or permucosal (ocular or mucous membrane) exposure to hepatitis B. If needed, HBIG and/or HBV should be given as soon as possible and at separate sites if both are given. In this setting the usefulness of giving them later than 1 week after exposure is not known. Two doses of HBIG are then 75% effective in preventing hepatitis B.

Individuals with hepatitis B and their contacts should also be evaluated for hepatitis C and HIV (if concomitant risk) and other STDs (with sexual exposure). The source person in a needle-stick injury should be evaluated for hepatitis C and abnormal liver function as well as HIV, especially if at high risk for these illnesses. The usefulness of giving pooled IG to prevent hepatitis C transmission is unknown. If HBIG is given, ideally an MMR vaccine should not be given until 3 months later and varicella vaccine not until 5 months later. For postexposure prophylaxis of HIV infection, see Chapter 32 .

[edit] Hepatitis A

Hepatitis A is spread from person to person through fecal contamination and oral ingestion. It is endemic in developing countries, and sporadic outbreaks occur in the United States. The clinically identifiable sources of spread are 22% to 26% household or sexual contacts, 14% child care settings, 6% travel, 2% to 3% food or water sources, 4% homosexual or bisexual men, and 3% injection drug users. In the U.S. population, 33% of adults have natural immunity, which increases with age and decreases with higher income. Natural immunity is even higher in developing countries. Prevaccination titers are probably cost-effective in persons from high-risk groups, those over age 40, and persons from developing countries.

The highest degree of viral shedding occurs 1 to 2 weeks before clinical illness and is minimal 1 week after the onset of jaundice. Any person with active disease should be excluded from attending day-care facilities, isolated if in a custodial institution, or furloughed from food-handling or health care employment until 1 week after the onset of symptoms or until the jaundice disappears, whichever is longer.

The hepatitis A vaccine is derived from purified viral antigens. The seroconversion rate after the first dose is 88% and after the second dose 100%. The vaccine is 95% to 100% effective in preventing clinical disease. The duration of immunity is at least 7 years. For travelers to high-risk countries, either vaccine or pooled IG is given. The vaccine is used when at least one dose can be given 4 weeks before departure. Otherwise, pooled IG is used: 0.02 ml/kg (3.3 mg IG/kg) IM for travel of 3 months or less; 0.06 ml/kg (10 mg IG/kg) IM for travel longer than 3 months, with revaccination every 5 months. Travelers should be educated to avoid exposure through careful food and water selection (see Travel). The vaccine is not recommended for persons who work with food or in child care because cases are sporadic in these settings.

Pooled IG (0.02 ml/kg IM) for postexposure prophylaxis of hepatitis A should be given as soon as possible and within 2 weeks of exposure. It is 85% effective in preventing disease and has its greatest effect early in the incubation period. When pooled IG is indicated and IM injection is contraindicated, as in patients with severe thrombocytopenia or a coagulation disorder (e.g., hemophilia), an intravenous preparation of 110 mg/kg can be used. Because these intravenous IG preparations are derived from smaller donor pools, they may not be as effective for hepatitis A. Therefore no specific recommendation exists.

Close household or sexual contacts of a person with acute hepatitis A should be given pooled IG. If a custodial institution has an outbreak of hepatitis A, selected staff in close contact with the index patient and clients should be given pooled IG. Co-workers of food handlers with hepatitis A should be given pooled IG. If a day-care center has an outbreak of hepatitis A, the staff and children as well as household contacts of diapered children should be given pooled IG. If pooled IG is given for hepatitis A prophylaxis, an MMR vaccine should not be given until 3 months later and varicella vaccine not until 5 months later.

The hepatitis A vaccine is not recommended for postexposure prophylaxis but has been useful in reducing cases during disease outbreaks in some populations.

[edit] Pneumococcus

Pneumococcal disease in the United States annually causes an estimated 150,000 to 570,000 cases of pneumonia, 2600 to 6200 cases of meningitis, and about 40,000 deaths. The mortality is highest in elderly people, patients with debilitating medical illnesses, and those who develop either meningitis or bacteremia. Pneumococcal disease in combination with influenza is the sixth leading cause of death in the United States. Up to two thirds of patients hospitalized with serious pneumococcal disease have been hospitalized in the previous 4 years and have not been vaccinated as recommended. With the emergence of drug-resistant strains of bacteria, prevention of disease has become even more important. Despite recommendations, vaccine rates are less than 30% in elderly persons.

The pneumococcal vaccine contains capsular antigens of the 23 types of Streptococcus pneumoniae that cause 88% of pneumococcal bacteremia. It is estimated to be at least 60% effective in preventing disease in immunocompetent adults older than 65 years. This degree of efficacy has been shown using cohort analysis for persons with diabetes, congestive heart failure, coronary vascular disease, and asplenia. Data for immunocompromised patients and those with alcoholism or cirrhosis suggest that the efficacy is less.

The vaccine's efficacy lasts for up to 9 years but is less in certain groups. Revaccination is recommended at 5 years for those who are most susceptible to a fatal disease or for those whose antibody levels decline at a rapid rate. It is also recommended at 5 years for persons vaccinated for any reason before age 65 and for those 65 years or older. Administration of more than two doses of the vaccine has not been studied and will be evaluated in the future.

[edit] Influenza

Influenza infection causes serious morbidity and mortality in the United States, especially in elderly persons and those with underlying medical illnesses. During influenza season, hospitalizations for comorbid conditions increase, and more cardiopulmonary deaths are associated with influenza and concomitant pneumonia. The average number of deaths attributable to influenza is estimated at 20,000 per year in the United States, with an estimated 110,000 hospitalizations. Up to 40,000 deaths occur during years with severe epidemics.

The efficacy of the influenza vaccine varies. In young healthy adults it is up to 90% effective in preventing disease, and it is cost-effective for employers to offer the vaccine to their workers. In elderly persons or those with chronic illnesses the antibody response can be much lower. In these individuals the vaccine is more effective in preventing lower tract disease and disease severity than the disease itself. The vaccine has been shown to be 50% effective in reducing influenza-related illnesses, 32% to 45% effective in preventing hospitalization, 31% to 65% effective in reducing hospital respiratory deaths, and 27% to 30% in reducing deaths from all causes. Despite this, 35% of adults over age 64 are not immunized each year.

Influenza A and B viruses are classified into subtypes according to two surface antigens: neuraminidase and hemagglutinin. Immunity to one subtype confers little or no protection against viruses of another subtype. Furthermore, antigenic variation within a subtype may occur, so vaccination with one strain may not protect against another distantly related strain of the same subtype. Because influenza season is April to September in the southern hemisphere and all year long in the tropics, worldwide surveillance and antigenic characterization of the circulating strains of influenza provide the basis for predicting which viral strains are most likely to cause illness in the United States in a given year. The inactivated vaccine, derived from two strains of influenza A and one strain of influenza B, contains either whole virus, viral antigen, or split virus (treated with lipid solvents), all initially grown in chicken embryos. The whole virus vaccine causes more febrile reactions in children and therefore is not recommended for them. Unlike the 1976 swine flu vaccine, no clear association exists between any subsequent influenza A and B vaccine and the Guillain-Barré syndrome.

Influenza season in the United States typically begins in December and peaks in January and February, so the vaccine is usually given from mid-October to early November. The vaccine can be used (1) as long as influenza is documented in a community and (2) as late as April. Antibodies to the influenza vaccine develop within 2 weeks. Although immunity typically lasts up to 10 months, it may last considerably less in medically ill or immunocompromised patients. Because immunity to the vaccine is short-lived and because strains of the virus in circulation may change, an annual vaccination is recommended. For treatment of susceptible individuals exposed to influenza A, see Chapter 33 .

[edit] Hemophilus Influenza b

Invasive disease caused by hemophilus influenza type b occurs mostly in childhood, with 85% of cases occurring in children under age 5 years. The vaccine is given routinely in pediatric practice. Invasive hemophilus influenza disease is rare in adults and occurs predominantly in those with conditions that predispose them to infection with encapsulated organisms. Even so, less than half of the invasive disease in these individuals is caused by the type b bacteria used in the vaccine.

The vaccine is derived from a type b capsular polysaccharide of hemophilus influenza type b. It is conjugated to protein carriers to induce a greater immune response. The protein carriers include diphtheria toxoid or the outer membrane protein complex of Neisseria meningitidis. The clinical efficacy in adults is not known and the need for boosters not established, but in splenectomy patients vaccinated 2 weeks preoperatively, the vaccine is immunogenic in 87%. For postexposure prophylaxis of hemophilus influenza type b, see Chapter 27 .

[edit] Meningococcus

In the United States, meningococcal disease occurs seasonally in late winter or early spring. It infects primarily children under age 5 years, with peak incidence between ages 6 and 12 months. One third of cases, however, occur in persons older than 20 years. The vaccine can be used to reduce the number of secondary cases during outbreaks if the responsible serogroups in the index case are represented by the vaccine. In the United States, serogroups B and C cause 30% and 50% of the cases respectively, and serotypes Y and W135 cause most of the rest.

The vaccine contains polysaccharides of N. meningitidis serotypes A, C, Y, and W135. The need for booster doses has not been studied, and the duration of protection varies for the individual serotypes; adults should be considered for revaccination in 3 to 5 years. For postexposure prophylaxis of N. meningitidis, see Chapter 27 .

[edit] Lyme Disease

Lyme disease, the most common vector-borne disease in the United States, is principally caused by Borrelia burgdorferi and transmitted by Ixodes ticks that normally feed on deer. The illness was described in Europe in the early 1900s and first described in the United States in 1970, although serologic studies identify it as far back as 1962. Since 1982, more than 100,000 cases have been reported, and the number increases each year. Cases are mostly from northeastern, mid-Atlantic, north-central, and western Pacific states, although the prevalence within states varies greatly. The primary risk for developing the disease is residing in or traveling to woodland or grassy areas that harbor the tick. Late spring and early summer are the peak times for transmission, when the nymphs emerge to feed, but the risk continues throughout the year as the adults feed. The ticks are about the size of a pinhead, depending on their age (see Chapter 94 ).

The vaccine is a recombinant DNA–derived lipoprotein, OspA, which is the most immunogenic of the bacterium's outer surface proteins. The clinical efficacy in preventing Lyme disease after two doses is 50% and after three doses 78%. After two doses, 99% of patients develop vaccine antibody, which wanes to 83% by the third dose. The third dose results in 100% seroconversion, which lasts at least 7 months. The duration of clinical efficacy is at least 2 years and is being evaluated further. The immune response to the vaccine can cause a positive immunoglobulin G enzyme-linked immunosorbent assay (IgG ELISA) in the absence of true disease; therefore a confirmatory test for disease exposure is required. Previous infection may not confer protective immunity. Persons should be instructed how to avoid tick exposure (see Travel).

[edit] Rabies

Since rabies in domesticated animals was controlled in the 1940s and 1950s, only two or three cases of human rabies are reported each year. An epidemic of rabies infection in certain wild animals has spread to many parts of the United States in recent years. In the United States, more than 85% of rabies transmission is through carnivorous wild animals, such as skunks, raccoons, foxes, coyotes, and bats, and except for the woodchuck, rarely through rodents. In developing countries, rabies is transmitted primarily through domesticated animals, primarily the dog; wild animals harbor it as well. Rabies is usually transmitted through a bite, but saliva in contact with open wounds or mucous membranes may transmit the disease. In addition, airborne transmission probably has occurred in bat caves. The incubation period for rabies is generally 10 to 90 days but can be up to 1 year. The infection is almost uniformly fatal.

The three licensed inactivated rabies vaccines are grown in (1) human diploid cells (HDCV), (2) rhesus lung cell cultures (RVA), and (3) chick embryo cell cultures (PCEC). Anaphylaxis occurs in 0.1% of recipients and is a reason to discontinue the primary series. The serum sickness–like reaction seen with HDCV may not occur with the other types of rabies vaccine. Chloroquine and similar compounds (e.g., mefloquine) can interfere with the immune response to rabies vaccine when it is given intradermally. Travelers planning to take these antimalarials should receive at least three doses of the intradermal vaccine before taking the medication. If this cannot be accomplished, the IM route should be used, giving as much of the series as possible. Immunocompromised individuals who receive preexposure prophylaxis should have an antibody titer checked 1 month after the series. Giving a booster dose or checking the titer is recommended every 2 years for any person with frequent exposure. Although substituting different vaccine preparations during a series is not recommended, booster doses from one type seem to produce an anamnestic response in another.

The local or state health department should be contacted about any questionable exposure to rabies. Wild animals and ill domesticated animals are killed, whereas healthy domestic animals are observed for 10 days. If a quarantined animal develops signs of rabies, if an animal that likely has rabies cannot be located, or if a killed animal is shown to harbor rabies, postexposure prophylaxis is given.

The postexposure treatment of rabies begins with local wound care. Because the virus may localize at the entry site for a time, wound care is extremely important in preventing the virus from entering neural tissue. All wounds should be flushed and cleaned with soap and water and should not be sutured if possible. Antibiotic prophylaxis for the bacteria associated with the animal's bite should also be given. Table 5-2 summarizes immunoprophylaxis. HRIG should be given as soon as possible, but average delays of 5 days have not been associated with failures. In a low-risk situation when laboratory analysis of the suspected animal will be available within 48 hours, postexposure prophylaxis may wait pending these results. If indicated, HRIG should be given within 7 days of the first vaccine because after that time the immune response to the vaccine is expected to occur and HRIG is less useful. The dose of HRIG should not exceed the recommended dose because this can interfere with the immune response to the vaccine. Immunocompromised persons should have antibody titers measured 2 to 4 weeks after postexposure prophylaxis. If HRIG is given, ideally an MMR vaccine should not be given until 4 months later and a varicella vaccine not until 5 months later.

[edit] Poliomyelitis

In the United States the incidence of poliomyelitis is low because of the maintenance of very high vaccination rates (95% of children) since the vaccine became available in the mid-1950s and early 1960s. The last polio epidemic occurred in 1979 in a group who refused vaccination. Since that time the only cases of poliomyelitis in the United States (less than 10 per year) have been vaccine associated, of which 78% occur after the first dose. Likewise, in other parts of the western hemisphere, no wild poliovirus infections have been reported since 1991. Poliomyelitis is much more prevalent in most developing countries. In temperate areas, poliomyelitis occurs primarily during summer and fall, but in the tropics it can occur at any time.

The polio vaccine is available as an inactivated trivalent virus vaccine (IPV) containing virus types 1, 2, and 3. The oral, live trivalent virus vaccine is no longer manufactured in the United States. The primary series of IPV is three doses. If time does not allow for three doses as specified, the vaccine should be given as a series of three doses, each a month apart, giving as many of the doses as possible before travel. The primary series should then be completed subsequently. If travelers have already received a primary series, they should be given a booster dose. The vaccine series is 95% effective in preventing clinical disease.

[edit] Typhoid

Approximately 450 cases of typhoid fever occur annually in the United States, 70% of which are acquired through foreign travel. Typhoid vaccine is recommended for certain travelers (see Table 5-7). Travelers should be educated to avoid exposure through careful food and water selection (see Travel). The vaccine is also recommended for persons having continued household contact with a known carrier and for laboratory workers handling the bacterium.

Several preparations of the vaccine are derived from the bacterium Salmonella typhi. The vaccine series is 70% to 90% effective. No data exist on the safety of these vaccines during pregnancy. The oral live vaccine should not be given to immunocompromised patients, but the inactivated vaccine theoretically is considered safe.

Because the oral typhoid vaccine is a live vaccine, certain principles apply (see Multiple Vaccines and Immune Globulins). Parenteral typhoid, cholera, and plague vaccines typically cause local or systemic reactions; therefore the simultaneous administration of these vaccines should be avoided if possible. The antimalarial mefloquine may interfere with the immune response to oral typhoid; therefore the vaccine should be given 24 hours before or after mefloquine. Likewise, oral antibiotics should not be given within 7 days of oral typhoid.

[edit] Yellow Fever

Yellow fever has been reported in central Africa and central South America (see Table 5-7). The virus is transmitted by mosquito vector. The vaccine is available only at an approved yellow fever vaccination center, which can be located by contacting the local health department. Vaccinated persons should receive a validated International Certificate of Vaccination. Failure to document prior vaccination may result in revaccination, quarantine, or refusal of entry. Travelers should also be educated on how to avoid mosquitoes (see Travel).

The vaccine is an attenuated live virus vaccine grown in chicken embryos. Booster doses are recommended every 10 years, although recent evidence suggests that serologic immunity lasts for at least 30 years.

If a pregnant woman or a woman planning to become pregnant within 3 months intends to travel to endemic areas, yellow fever vaccine can be given if travel plans cannot be delayed and exposure is imminent. Even though it is a live vaccine, there is no known risk to the fetus, and disease in the mother has serious morbidity and mortality. Yellow fever vaccine should not be given to immunocompromised or symptomatic HIV-infected patients, although no data exist on adverse reactions. If the risk of yellow fever is high, asymptomatic HIV-infected individuals should be advised of the risk vs. benefit of vaccination and given the choice of vaccination.

Yellow fever vaccine is a live virus vaccine, so special principles apply to its administration (see Multiple Vaccines and Immune Globulins). Yellow fever and cholera vaccines should be given at least 3 weeks apart; simultaneous administration can diminish the antibody response to both vaccines.

[edit] Japanese Encephalitis

The mosquito-borne Japanese encephalitis virus is the leading cause of viral encephalitis in Asia. This encephalitis also occurs in the Indian subcontinent and in Oceania. The viral infection appears most often in native populations and leads to encephalitis in one of 20 to 1000 cases, with death occurring in 25% of those infected and neurologic sequelae in 30%. By adulthood, almost everyone in endemic countries has serologic evidence of exposure. The virus is transmitted seasonally in temperate regions, mainly during summer and early fall. In tropical areas, transmission can be year-round. The risk of acquiring infection is low for most travelers to these areas. However, the vaccine is recommended for travelers spending at least a month during the transmission season, especially if traveling in rural areas, and for those spending less time but most of it outdoors in rural areas (see Table 5-7). Travelers should also be educated about mosquito bites (see Travel).

The vaccine is composed of inactivated virus derived from virus-infected mouse brain. If there are time constraints and the recommended series cannot be completed, the vaccine can be given on days 0, 7, and 14. The vaccine is 80% to 90% effective in preventing encephalitis. A serious reaction to the vaccine consists of generalized urticaria and angioedema, which can occur up to 2 weeks postvaccination and at a rate of five in 1000 patients. Medications to treat anaphylaxis should be on hand at the vaccination, and the recipient should be observed for 30 minutes. Recipients should be warned of the symptoms of anaphylaxis and advised to seek medical attention if any occur in the ensuing weeks. Individuals with a history of hypersensitivity phenomena appear to be at increased risk. Vaccine-associated encephalitis is rare; only one or two cases per million vaccines have been documented. The need for booster doses is unknown, but immunity appears to last for at least 2 years.

[edit] Cholera

Cholera is a risk to travelers in more remote areas of Africa, Asia, and Latin America. The vaccine series is recommended for travelers to these countries who are at high risk. Although no country currently requires the vaccine, some local authorities may require it (see Table 5-7). The current vaccine series is only 50% effective in preventing clinical illness for 3 to 6 months. Travelers should be educated to avoid exposure through careful food and water selection (see Travel).

The vaccine is derived f