II Immunology/Vaccinology Flashcards
BCG (Indications/contraindications, routes of administration, dosing regimens duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications: used once at birth in most developing countries to reduce the severe consequences of TB in infants and children. for persons at high risk of repeated exposure, for certain long-term travellers to high prevalence countries, and in infants born to mothers with infectious TB disease.
Route and regimen: ID - Live Vaccine Infants (12 months of age and younger): 0.05 mL (0.05 mg) Children (greater than 12 months of age) and adults: 0.1 mL (0.1 mg)
Duration of Protection: The duration of BCG vaccine protection is not well-established. Although generally thought to have declining protection over time, one follow up study demonstrated a protective effect for as long as 60 years. BCG vaccine will not prevent the development of active TB in individuals who are already infected with M. tuberculosis.
Immunogenicity and efficacy:
Clinical trials have demonstrated conflicting results regarding BCG vaccine’s efficacy. Meta-analytic reviews have estimated the vaccine efficacy in preventing any TB disease at approximately 51%. The protective effect of BCG vaccine against disseminated TB in the newborn is estimated to be 78%.
AE:
Intradermal administration of BCG vaccine usually results in the development of erythema and either a papule or ulceration (in about 50%), followed by a scar at the immunization site. Keloid formation occurs in 2% to 4% of vaccine recipients. Non-suppurative regional lymphadenopathy occurs in 1% to 10%. Most reactions are generally mild and do not require treatment. Other: BCG immunization may result in a positive TST. The benefits gained by immunization must be weighed against the potential loss of the TST as a primary tool to identify infection with M. tuberculosis. The increasing availability of interferon gamma release assay (IGRA) blood testing may reduce this concern because the BCG vaccine does not produce a “false positive” result with the IGRA test.
Cholera (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications: Travellers to cholera-endemic countries who may be at significantly increased risk of exposure (e.g., humanitarian workers or health professionals working in endemic countries) may benefit from immunization with cholera and travellers’ diarrhea vaccine. Most travellers following the usual tourist itineraries in countries affected by cholera are at extremely low risk of acquiring cholera infection.
Routes and dosing: Primary: 6 yo and older: 2 doses orally, 1-6 weeks apart If more than 6 weeks elapses between doses, re-peat primary series. Give final dose at least 1 week before departure
Booster: 1 dose every 2 years. If more than 5 years have passed since primary immunization or last booster dose, repeat primary series.
Duration of protection: 2 years
Immunogenicity & Efficacy: An overall efficacy against V. cholerae O1 El Tor of 64% and complete protection against moderate to severe diarrhea. A large field trial using an early formulation of this vaccine demonstrated efficacy of 85% against V. cholerae O1 El Tor disease for the initial 6 months and 50% for the 3-year follow-up period. A field trial using the current cholera and travellers’ diarrhea vaccine demonstrated an efficacy of 86% against epidemic cholera. Cholera and travellers’ diarrhea vaccine does not protect against cholera caused by V. cholerae O139 or other species of Vibrio. Protection against cholera can be expected approximately one week after completion of primary immunization and lasts for 2 years in persons 6 years of age and older, and 6 months in children 2 to 5 years of age.
Adverse effects:
abdominal pain (16%), diarrhea (12%), nausea (4%) and vomiting (3%). These events are most likely due to the bicarbonate buffer used with the vaccine since they occurred with similar frequency when vaccine and buffer or buffer alone were given.
Diphtheria (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications:
Everyone > 2 months
route of administration: IM, combination vaccines
Dosing regimen: administer DTaP-IPV-Hib vaccine at 2, 4, 6 and 12 to 23 months of age Adults previously immunized with diphtheria-toxoid containing vaccine: administer one dose of Tdap vaccine if the patient has not previously received this vaccine in adulthood (18 years of age and older) and give a booster dose of Td vaccine every 10 years
Duration: 10 years
Efficacy:
After a complete primary series, more than 97% of vaccinees develop antibody concentrations that are protective against diphtheria toxin. In studies assessing booster response, 100% of vaccinees had a protective antibody titre one month after the booster dose. Antitoxin is believed to persist at protective concentrations for 10 years or more.
Adverse reactions:
Redness, swelling and pain at the injection site are the most common adverse reactions to childhood diphtheria toxoid-containing combination vaccines. A nodule may be palpable at the injection site and persist for several weeks. Abscess at the injection site has been reported. In clinical trials, injection site adverse reactions, including tenderness, erythema, swelling or any combination of these findings, were reported in 10% to 40% of children after each of the first 3 doses of diphtheria-toxoid containing vaccine. Mild systemic reactions such as fever, irritability fussiness or any combination of these findings were commonly reported (8% to 29%), as well as drowsiness (40% to 52%). Among adults given a booster dose of Tdap vaccine, common reactions include pain, redness and swelling at the injection site, headache, and fatigue. Fever and chills also are common reactions. Adverse reactions following Td vaccine are similar. Overall, adverse reactions are less common in adults than adolescents. The interval between the childhood DTaP vaccine series or a dose of Td vaccine, and a dose of Tdap vaccine does not affect the rate of injection site or systemic adverse events.
Japanese Encephalitis (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications:
When making recommendations regarding the use of JE vaccine for travelers, clinicians must weigh the overall low risk of travel-associated JE, the high rate of death and disability when JE occurs, the low probability of serious adverse events after immunization, and the cost of the vaccine. Evaluation of a traveler’s risk should take into account the planned itinerary, including travel location, duration, activities, and seasonal patterns of disease in the areas to be visited. The data in the table should be interpreted cautiously, because JE virus transmission activity varies within countries and from year to year.
The Advisory Committee on Immunization Practices recommends JE vaccine for travelers who plan to spend ≥1 month in endemic areas during the JE virus transmission season. This includes long-term travelers, recurrent travelers, or expatriates who will be based in urban areas but are likely to visit endemic rural or agricultural areas during a high-risk period of JE virus transmission. Vaccine should also be considered for the following:
Short-term ( Travelers to an area with an ongoing JE outbreak.
Travelers to endemic areas who are uncertain of specific destinations, activities, or duration of travel.
JE vaccine is not recommended for short-term travelers whose visits will be restricted to urban areas or times outside a well-defined JE virus transmission season.
Routes and dosing:
0.5mL (IM)
A series of two doses given on days 0 and 28 should be administered. The immunization series should be completed 10 to 14 days before potential exposure to JE to develop an adequate antibody response. An accelerated schedule is not available. However, if there is insufficient time to administer the recommended two-dose schedule before entering a JE risk situation, a single dose of JE vaccine may be considered and the vaccinee advised that protection against JE may not be reliable. Alternatively, simultaneous administration of two doses of JE vaccine (given with separate injections at separate injection sites) may be considered; however, the risks and benefits of this approach must be critically evaluated.
Duration:
A booster dose (third dose) should be given one year after the second dose in the primary series, when there is a potential for re-exposure to JE virus. Persons at continuous risk for acquiring JE (laboratory personnel or persons residing in endemic areas) should receive a booster dose 12 months after primary immunization. Data on the need for further booster doses are not available. If a person received the previous mouse brain-derived JE vaccine more than 3 years ago and requires re-immunization, a two dose primary series of the currently available Vero cell culture-derived JE vaccine (IXIARO®) should be administered.
Efficacy/immunogenicity:
No efficacy or effectiveness data exist for the Vero cell culture-derived JE vaccine, IXIARO®. IXIARO® was authorized for use based on non-inferiority of serologic response compared to the previous mouse brain-derived JE vaccine and to the WHO threshold for protective antibody titre.
A single dose of JE vaccine induces sufficient protective antibodies in 30% of vaccinees at 10 days after vaccination and in 40% of vaccinees at 28 days post-vaccination. A second dose of vaccine given at 28 days after the first dose induces antibodies in about 95% of vaccinees at 28 days after the second dose. Vaccination with two doses of vaccine at the same time may increase the seroconversion rate to 60% at 10 days post-vaccination. The protective antibody concentration declines over time with 80% to 95% of fully immunized vaccinees maintaining an adequate concentration at 6 months after the first dose and 60% to 80% maintaining adequate antibodies at 12 months after the first dose. A booster dose of vaccine, among those who have completed a properly spaced primary series, induces an adequate antibody concentration in those who have lost protective antibodies at 12 months after their first dose.
Adverse effects:
Local symptoms of pain and tenderness were the most commonly reported symptoms in a safety study with 1,993 adult participants who received 2 doses of Ixiaro. Headache, myalgia, fatigue, and an influenzalike illness were each reported at a rate of >10%. In children, fever was the most commonly reported systemic reaction in studies. Because Ixiaro was licensed after study in
Tick Borne Encephalitis (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications:
TBE is endemic in focal areas of Europe and Asia (from eastern France to northern Japan and from northern Russia to Albania). Most cases occur from April through November, with peaks in early and late summer when ticks are active. The incidence and severity of disease are highest in people aged ≥50 years. Travelers anticipating high-risk exposures, such as working or camping in forested areas or farmland, adventure travel, or living in TBE-endemic countries for an extended period of time, may wish to be vaccinated in Canada or Europe. Because the routine primary vaccination series requires ≥6 months for completion, most travelers to TBE-endemic areas will find avoiding tick bites to be more practical than vaccination.
Routes of administration: IM: 0.5 mL days 0, 1-3 months, 6-15 months > 15 years of age
Duration of protection Booster: First booster: 3 years Subsequent boosters: 5 years
Immunogenicity/Effiacy:
Immunogenicity studies suggest that the European and Russian vaccines should provide cross-protection against all 3 TBEV subtypes. For both FSME-IMMUN and Encepur, the primary vaccination series consists of 3 dose Although no formal efficacy trials of these vaccines have been conducted, indirect evidence suggests that their efficacy is >95%. Vaccine failures have been reported, particularly in people aged ≥50 years.
Adverse effects
In adults and children, adverse reactions are typically transient local reactions classified as mostly mild to moderate. Fever and other systemic reactions, such as headaches, malaise, dizziness, anorexia, nausea, vomiting, diarrhea, and myalgia are also reported in a small proportion of vaccinees.
Hib (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications:
Travellers Unimmunized or incompletely immunized travellers should receive diphtheria-tetanus-pertussis-polio-Hib-containing vaccine as appropriate for age. Hib-containing vaccine is recommended for routine immunization of infants and children 2 to 59 months of age (up to the fifth birthday). Hib vaccine is recommended for individuals (5 years of age and older) with: congenital (primary) immunodeficiency; malignant hematologic disorders; HIV; anatomic or functional asplenia, including sickle cell disease; all transplant recipients; and cochlear implant recipients.
Route and regimen:
(IM) administer DTaP-IPV-Hib vaccine at 2, 4, 6 and 12 to 23 months of age (generally given at 18 months of age) Children 5 years of age and older or adults with chronic conditions with increased risk of invasive Hib disease: administer a single dose of Hib vaccine, even if previously vaccinated when younger, with at least one year from a previous dose.(congenital (primary) immunodeficiency; malignant hematologic disorders; HIV; anatomic or functional asplenia (including sickle cell disease); all transplant recipients; and cochlear implant recipients)
Duration of protection
The duration of immunity following completion of age-appropriate immunization is unknown, but data suggest that protection is long lasting.
Immunogenicity/Efficacy
Clinical efficacy of Hib vaccination has been estimated at 95% to 100%. A significant component of protection of children arises because of herd immunity and so relies upon good vaccination coverage.
Potential Adverse effects
Injection site reactions, including pain, redness and swelling, occur in 5% to 30% of children immunized with Hib vaccine. These symptoms are mild and usually resolve within 24 hours. Fever has been reported in some infants given Hib vaccine, either alone or in combination with other vaccines.
Hepatitis A (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications:
All susceptible people traveling for any purpose, frequency, or duration to countries with high or intermediate HAV endemicity should be vaccinated or receive IG before departure. Currently, international travel is considered the number one risk factor for HAV infection in the United States. Although the Advisory Committee for Immunization Practices recommends hepatitis A vaccination for people traveling to countries with high or intermediate HAV endemicity, published maps may not be the best guide in determining endemicity in developing countries. Prevalence patterns of HAV infection may vary among regions within a country, and missing or obsolete data present a challenge. Countries where the prevalence of HAV infection is decreasing have increasing numbers of susceptible people, and there is a risk of large outbreaks of hepatitis A. In addition, in recent years, large outbreaks of hepatitis A were reported in developed countries among people who had been exposed to either food handlers with hepatitis A or imported food contaminated with HAV. Taking into account the complexity involved with interpreting hepatitis A risk maps and potential foodborne hepatitis A risk in countries with low endemicity, some expert travel clinicians advise people traveling outside the United States to consider hepatitis A vaccination regardless of their destination. Vaccination is recommended for unvaccinated household members and other people who will have close personal contact (such as regular babysitters) with an international adoptee from a country of high or intermediate endemicity
route: (IM) 0, 6-12 months can vary based on manufacturer. Dose 1-18 years is 0.5 mL and 1.0mL for >18
Duration of protection: Long term with 2 doses
Efficacy: Pre-exposure HA vaccines have demonstrated at least 90% to 97% effectiveness in preventing clinical illness. Post-exposure Epidemiologic studies of HA outbreaks have shown that the use of vaccine in the susceptible population interrupts the outbreak. The protective efficacy of vaccine in one study when vaccine was used within one week of exposure was 79%.
Adverse effects:
Among adults, the most frequently reported side effects, occurring 3–5 days after a vaccine dose, are tenderness or pain at the injection site (53%–56%) or headache (14%–16%). Among children, the most common side effects reported are pain or tenderness at the injection site (15%–19%), feeding problems (8% in one study), or headache (4% in one study). No serious adverse events in children or adults have been found that could be attributed definitively to the vaccine, nor have increases in serious adverse events been identified among vaccinated people compared with baseline rates.
Hepatitis B (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications:
Hepatitis B vaccination should be administered to all unvaccinated people traveling to areas with intermediate to high prevalence of chronic hepatitis B (HBV surface antigen prevalence ≥2%). Vaccination may be considered for all international travelers, regardless of destination, depending on the traveler’s behavioral risk as determined by the provider and traveler.
Route and dose: (IM) Hepatitis B vaccine is usually administered as a 3-dose series on a 0-, 1-, 6-month schedule to achieve immunity. The second dose should be given ≥1 month after the first dose; the third dose should be given ≥2 months after the second dose and ≥4 months after the first dose. The third dose should not be given before age 24 weeks. Exceptions to this schedule are available with specific licensed products in the United States; Recombivax HB (Merck & Co.) is licensed for a 2-dose schedule for children aged 11–15 years, and Engerix-B (GlaxoSmithKline) is licensed for a 4-dose schedule (0, 1, and 2 months, plus a 12-month booster) The accelerated vaccination schedule calls for vaccine doses administered at days 0, 7, and 21–30; a booster should be administered at 12 months to promote long-term immunity. A combined hepatitis A and hepatitis B vaccine can also be used on the same 3-dose schedule (0, 7, 21–30 days).
Duration of protection: In endemic regions, the duration of protection induced by vaccination has been shown to be at least 15 years in most vaccinees.
Immunogenicity and efficacy
Pre-exposure HB vaccine is 95% to 100% effective in preventing HB in people who receive a complete vaccine series. Post-exposure HB vaccination and one dose of hepatitis B immune globulin (HBIg) administered within 24 hours after birth are 85% to 95% effective in preventing HB infection in exposed neonates. Studies have demonstrated the efficacy of HBIg and HB vaccine in percutaneous or mucosal exposure to HB-positive blood, or sexual exposure to HB-positive persons. A single dose of HBIg is 75% effective if administered within 2 weeks of last sexual exposure. The major determinant of seroprotection rates achieved is the age at vaccination, but outcome also varies with the schedule used, the dosage, and the health of the vaccinee. While children less than 2 years of age have a 95% response rate, the best response is observed in children between the ages of 5 and 15 years with 99% seroprotection rates. Generally, the response rate for adults decreases with age. The antibody response is lower in patients with diabetes mellitus (70% to 80%), renal failure (60% to 70%), and chronic liver disease (60% to 70%). Immunization of obese people, smokers and those with alcoholism may also produce lower antibody titres. Immunocompromised patients, such as those infected with HIV, will have a diminished response in proportion to the level of immune deficiency. Most people undergoing dialysis do not respond well to HB vaccine and do not develop an immune memory.
Adverse Drug Reactions: HB vaccine is well tolerated. Reactions are usually mild and transient, and include irritability, headache, fatigue and injection site reactions (e.g., pain and redness) in 10% or more of recipients.
Human Papilloma Virus (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications:
HPV2 or HPV4 vaccine is recommended for prevention of cervical cancer in girls and women 9 to 26 years of age, including those who have had previous Papanicolaou [Pap] test abnormalities, cervical cancer or genital warts. HPV4 vaccine is recommended for the prevention of vulvar, vaginal, anal cancers and their precursors and anogenital warts in girls and women, 9 to 26 years of age. HPV2 or HPV4 vaccine may be administered to women 27 years of age and older at ongoing risk of exposure. HPV4 vaccine is recommended for prevention of anogenital cancer and genital warts in boys and men 9 to 26 years of age. HPV4 vaccine may be administered to men 27 years of age and older at ongoing risk of exposure. HPV2 vaccine is not approved for use in boys and men.
Route and schedule: (IM) HPV2 vaccine Immunocompetent, non-HIV infected, adolescents 9-14 years of age: Administer at months 0 and 6-12 or months 0, 1 and 6 HPV4 vaccine Immunocompetent, non-HIV infected, adolescents 9-14 years of age: Administer at months 0 and 6-12 or months 0, 2 and 6.
Duration of protection: Re-immunization with HPV vaccine is not indicated at this time, as protection lasts at least 7 years. If monitoring suggests that booster doses may be required, this matter will be reviewed by NACI.
Immunogenicity and efficacy
HPV vaccine is highly effective for the prevention of HPV vaccine type-related persistent infection and cervical cancer. In women 16 to 26 years of age, the efficacy of HPV4 vaccine against HPV types 16 and 18-related cervical disease is nearly 100%; efficacy against external genital lesions related to HPV types 6, 11, 16, or 18, including genital warts, is 95% to 99%. In men 16 to 26 years of age, HPV4 vaccine efficacy against vaccine type-related external genital lesions is 84% to 100%; efficacy against persistent vaccine-type related infection is 70% to 96% HPV vaccine is highly immunogenic. More than 99% of recipients develop an antibody response to vaccine HPV types after completing the three-dose series
Adverse effects: the most common adverse events in persons receiving HPV vaccine were vaccination site pain (82% to 92%), swelling (24% to 44%) or redness (24% to 48%). These adverse events were observed significantly more often following HPV vaccine than following active vaccine or placebo controls (which included hepatitis A or hepatitis A/hepatitis B vaccine, aluminum phosphate or saline). In over 94% of subjects who received HPV vaccine, the reactions were mild to moderate in intensity, resolved over a few days, and did not prevent completion of the immunization schedule. Systemic adverse events, such as fatigue, myalgia, headache, fever, and nausea, generally occurred with comparable frequency in vaccine and control groups.
Immune globulin (summary from NACI)
Passive immunizing agents are preparations containing pre-formed antibodies derived from humans or animals, or produced by recombinant DNA technology . Administration of passive immunizing agents can prevent certain infections or reduce the severity of illness caused by the infectious agent. Specific types of immune globulin Botulism antitoxin Botulism Ig Cytomegalovirus Ig Diphtheria antitoxin Hepatitis B Ig Rabies Ig Respiratory syncytial virus antibody (palivizumab) Tetanus Ig Vaccinia Ig Varicella zoster Ig Standard immune globulin: Standard human immune globulin (GamaSTAN® S/D) is a sterile, concentrated solution for intramuscular (IM) injection containing 15% to 18% immune globulin. It is obtained from pooled human plasma from screened donors and contains mainly IgG with small amounts of IgA and IgM. The potency of each lot of immune globulin product is tested against international standards or reference preparations for at least two different antibodies, one viral and one bacterial.
Maximum plasma levels are reached approximately 2 days after IM injection, and the half-life in the circulation of individuals with normal IgG levels is 23 days.
Recommendations for Use: Prophylactic use of IM Ig has been shown to be effective in a limited number of clinical situations, including exposure to measles and hepatitis A. The dose varies by indication, and recommendations in the product leaflet or product monograph should be followed. Measles: administered within 6 days after exposure to measles, however, it should be given as soon as possible after exposure when indicated. Ig should be considered for susceptible pregnant women and susceptible immunocompromised contacts of measles, and for children less than 6 months of age
The recommended dose of Ig for healthy individuals exposed to measles is 0.25 mL/kg of body weight given by the IM route. The dose for exposed individuals who are immunocompromised is 0.5 mL/kg of body weight. A maximum dose of 15 mL should not be exceeded. Hepatitis A Pre-exposure prophylaxis Hepatitis A (HA) vaccine is the preferred agent for pre-exposure prophylaxis. Ig will provide protection against HA when administered IM before exposure. Ig is indicated for pre-exposure prophylaxis for: infants less than one year of age persons with a history of anaphylaxis after previous administration of the HA vaccine and those with proven immediate or anaphylactic hypersensitivity to any component of the HA vaccine or its container immunocompromised persons. Immunocompromised people should receive Ig in addition to HA vaccine because they may not respond fully to the vaccine. Administering Ig immediately before travel will ensure that protective concentrations of antibody are adequate for short-term (up to 6 months) travel.
The recommended dose of Ig varies according to the duration of required protection. In general, for protection lasting less than 3 months the dose is 0.02 mL/kg of body weight. If protection is required for 3 months or longer, 0.06 mL/kg of body weight should be administered and repeated every 6 months. Post-exposure prophylaxis Hepatitis A (HA) vaccine is the preferred agent for post-exposure prophylaxis. Ig is the recommended post-exposure immunoprophylactic agent: for infants less than one year of age for persons with a history of anaphylaxis after previous administration of the HA vaccine and those with proven immediate or anaphylactic hypersensitivity to any component of the HA vaccine or its container if HA vaccine is unavailable for immunocompromised persons. Immunocompromised people should receive Ig in addition to HA vaccine because they may not respond fully to the vaccine.
Administration: Large volumes of immune globulin for IM injection (greater than 2 mL for children or greater than 3-5 mL for adults, depending on muscle mass) should be divided and injected at two or more sites. Adverse effects: Injection site reactions following receipt of standard human Ig include tenderness, erythema and stiffness of local muscles, which may persist for several hours. Mild fever or malaise may occasionally occur.
Other: Passive immunization with human Ig preparations can interfere with the immune response to MMR, measles-mumps-rubella-varicella (MMRV) and univalent varicella vaccines. These vaccines should be given at least 14 days prior to administration of a human Ig preparation, or delayed until the antibodies in the Ig preparation have degraded.
Influenza (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Annual influenza vaccination for those aged ≥6 months is the most effective way to prevent influenza and its complications.
Two types of influenza vaccines are available for use in the United States: trivalent inactivated vaccine (TIV) and trivalent live attenuated influenza vaccine (LAIV). TIV can be administered by intramuscular or intradermal injection and is available for people ≥6 months of age. Specific age indications vary by manufacturer and product; label instructions should be followed. For adults aged ≥65 years, a high-dose TIV is also available, containing higher levels of antigen. LAIV, administered by nasal spray, is approved for use only in healthy people aged 2–49 years who are not pregnant. Within indicated groups for each vaccine, there is no preference for TIV, high-dose TIV, or LAIV. In February 2012, the Food and Drug Administration approved the first quadrivalent LAIV (approved for ages 2–49 years), which is administered by nasal spray.
In the United States, annual influenza vaccination is recommended by the Advisory Committee on Immunization Practices for all US residents aged ≥6 months who do not have contraindications. Vaccination of pregnant women and household contacts of children aged
Routes of admin and dose:
- 5mL IM
- 1 ml 1 spray in each nostril
Children 6 months to less than 9 years of age who have never received the seasonal influenza vaccine require two doses of influenza vaccine, with a minimum interval of four weeks between doses. Eligible children less than 9 years of age who have properly received one or more doses of seasonal influenza vaccine in the past should receive one dose per influenza vaccination season thereafter.
Duration: Annual
Immunogenicity/Efficacy
Multiple studies show that influenza vaccine is efficacious, with higher efficacy demonstrated against laboratory-confirmed influenza than clinically defined outcomes. In healthy children a systematic review and meta-analyses showed that efficacy of influenza vaccine against laboratory confirmed influenza ranged from 59% to 82%, efficacy against serologically-confirmed influenza ranged from 54% to 63% and efficacy against clinical illness ranged from 33% to 36%. Similarly, a literature review conducted in 20l3 that looked at influenza vaccine effectiveness in healthy 5-18 year olds found that vaccine efficacy against laboratory confirmed influenza was variable but most frequently between 65-85%. In young children up to six years of age, there is evidence that LAIV protects better than TIV, with less evidence in older children.
In a systematic review, for healthy adults, inactivated influenza vaccine efficacy against laboratory-confirmed influenza was 80% (95% CI, 56 to 91), and vaccine effectiveness against influenza-like illness was 30% (95% CI, 17 to 41) when the vaccine strain matched the circulating strains. Another meta-analysis identified vaccine efficacy of 50% in healthy adults (95% CI, 27 to 65) during select seasons of vaccine mismatch, although mismatch is a relative term and the amount of cross-protection is expected to vary. In the elderly, vaccine effectiveness is about half of that of healthy adults.
In observational studies, influenza vaccine has been shown to reduce the number of physician visits, hospitalizations and deaths in high-risk persons 18 to 64 years of age, hospitalizations for cardiac disease and stroke in the elderly, and hospitalization and deaths in persons with diabetes mellitus 18 years of age and older.
Because influenza viruses change over time, immunity conferred in one season will not reliably prevent infection by an antigenically drifted strain. Even if the vaccine strains have not changed, immunity generally wanes within a year of receiving the vaccine and re-immunization reinforces optimal protection for the coming influenza season. Repeated annual administration of influenza vaccine has not been demonstrated to impair the immune response of the recipient to influenza virus.
Both humoral and cell-mediated responses are thought to play a role in immunity to influenza. While humoral immunity is thought to play a primary role in protection against infection, cell-mediated immunity, notably cytotoxic T lymphocyte responses to internal viral components, is increasingly invoked as important in protecting against severe outcomes of influenza, particularly those associated with subtype HA variations, both shift and drift.
Immunogenicity against the strains included in the influenza vaccine is typically measured by comparing the pre-vaccination and post-vaccination hemagglutinin inhibition (HI) antibody titres. The antibody response after vaccination depends on several factors, including the age of the recipient, prior and subsequent exposure to antigens and the presence of immune compromising conditions. Humoral antibody levels, which correlate with vaccine protection, are generally achieved by two weeks after immunization; however, there may be some protection afforded before that time.
Adverse Effects:
TIV
The most frequent side effects of vaccination with intramuscular and intradermal TIV in adults are soreness and redness at the vaccination site. These local reactions are slightly more common with intradermal vaccine and high-dose TIV. They generally are mild and rarely interfere with the ability to conduct usual activities. Fever, malaise, myalgia, and other systemic symptoms sometimes occur after vaccination; these may be more frequent in those with no previous exposure to the influenza virus antigens in the vaccine (such as young children) and are generally short-lived.
Guillain-Barré syndrome (GBS) was associated with the 1976 swine influenza vaccine, with an increased risk of 1 additional case of GBS per 100,000 people vaccinated. None of the studies of influenza vaccines other than the 1976 influenza vaccine has demonstrated a similar increase in GBS. Currently, the estimated risk for vaccine-related GBS is low, approximately 1 additional case per 1 million vaccinated.
LAIV
The most frequent side effects of trivalent and quadrivalent LAIV reported in healthy adults include minor upper respiratory symptoms, runny nose, and sore throat, which are generally well tolerated. Some children and adolescents have reported fever, vomiting, myalgia, and wheezing. These symptoms, particularly fever, are more often associated with the first administered LAIV dose and are self-limited.
LAIV should not be administered to any child aged
Measles (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications:
Measles vaccine contains live, attenuated measles virus. In the United States, it is available only in combination formulations, such as measles-mumps-rubella (MMR) and measles-mumps-rubella-varicella (MMRV) vaccine. MMRV vaccine is licensed for children aged 12 months to 12 years and may be used in place of MMR vaccine if vaccination for measles, mumps, rubella, and varicella is needed.
International travelers, including people traveling to industrialized countries, who do not have presumptive evidence of measles immunity and who have no contraindications to MCV, should receive MCV before travel according to the following guidelines:
Infants aged 6–11 months should receive 1 MCV dose. Infants vaccinated before age 12 months must be revaccinated on or after the first birthday with 2 doses of MCV separated by ≥28 days. MMRV is not licensed for children aged Preschool and school-age children (aged ≥12 months) should be given 2 MCV doses separated by ≥28 days.
Adults born in or after 1957 should be given 2 MCV doses separated by ≥28 days.
One dose of MCV is approximately 85% effective if administered at age 9 months and up to 95% effective if administered at age ≥1 year. More than 99% of people who receive 2 doses of MCV develop serologic evidence of measles immunity.
MCV and immune globulin (IG) may be effective as postexposure prophylaxis. MCV, if administered within 72 hours after initial exposure to measles virus, may provide some protection. If the exposure does not result in infection, the vaccine should induce protection against subsequent measles virus infection. IG can be used to prevent or mitigate measles in a susceptible person when administered within 6 days of exposure. However, any immunity conferred is temporary unless modified or typical measles occurs, and the person should receive MCV 5–6 months after IG administration.
Routes and dose:
0.5mL SC
Children (12 months to 12 years of age)
For routine immunization of children aged 12 months to 12 years, two doses of measles-containing vaccine (MMR or MMRV) should be administered. The first dose of measles-containing vaccine should be administered at 12 to 15 months of age and the second dose at 18 months of age or any time thereafter, but should be given no later than around school entry.
The recommended minimum interval between doses of MMR vaccine is 4 weeks. Children who previously received a single dose of MMR vaccine should receive a second dose at least 4 weeks after the first dose. The recommended interval between two doses of MMRV vaccine is at least 3 months; a minimum interval of 6 weeks between doses may be used if rapid, complete protection is required.
Adolescents (13 to 17 years of age)
Measles-susceptible adolescents should receive two doses of MMR vaccine given at least 4 weeks apart.
Adults (18 years of age and older)
Measles-susceptible adults should receive one or two doses of MMR vaccine as appropriate for age and risk factors. If two doses are needed, MMR vaccine should be administered with a minimum interval of 4 weeks between doses.
Duration of Protection:
Re-immunization with measles-containing vaccine after age and risk appropriate vaccination is not necessary.
Efficacy/Immunogenicity:
The efficacy of a single dose of measles-containing vaccine given at 12 or 15 months of age is estimated to be 85% to 95%. With a second dose, efficacy in children approaches 100%. However, measles outbreaks have occurred in populations with high immunization coverage rates. Due to the high infectivity of measles (each case may infect 12 to 18 others) at least 95% of the population needs to be immunized to develop herd immunity. There are no data regarding the efficacy of MMRV vaccine.
In clinical studies a single injection of MMR vaccine induced measles antibodies in 95%, mumps antibodies in 96%, and rubella antibodies in 99% of previously seronegative children.
In a study of 12 month old children, a single dose of MMRV vaccine resulted in a seroconversion rate for measles, mumps, rubella and varicella of 98%, 97%, 98% and 93%, respectively. The seroconversion rates and geometric mean titres for individual components were not significantly different from those achieved after MMR plus univalent varicella vaccines or MMR vaccine alone. A study of children receiving two doses of MMRV vaccine during the second year of life noted seropositivity for measles, mumps, rubella and varicella of 99%, 97.4%, 100% and 99.4% respectively by the third year post-vaccination. Long-term persistence of anti-measles, anti-mumps, anti-rubella and anti-varicella antibodies following MMRV vaccinations are under evaluation.
Adverse effects:
MMR vaccine
Adverse events following MMR immunization occur less frequently and are less severe than those associated with natural disease. Adverse reactions are less frequent after the second dose of vaccine and tend to occur only in those not protected by the first dose. Six to 23 days after MMR immunization, approximately 5% of immunized children experience malaise and fever (with or without rash) lasting up to 3 days. Parotitis, rash, lymphadenopathy, and joint symptoms also occur occasionally after MMR immunization.
MMRV vaccine
Pain and redness at the injection site or low-grade fever occur in 10% or more of vaccinees. Rash, including measles-like, rubella-like and varicella-like rash, as well as swelling at the injection site and moderate fever (greater than 39°C) occur in 1% to less than 10% of vaccinees. As varicella-like rashes that occur within the first two weeks after immunization may be caused by wild-type virus, health care providers should obtain specimens using viral transport media from a lesion to ensure varicella disease is not confused with a reaction to vaccination.
Rubella-containing vaccines
Acute transient arthritis or arthralgia may occur 1 to 3 weeks after immunization with rubella-containing vaccine, lasts for about 1 to 3 weeks, and rarely recurs. This is more common in post-pubertal females, among whom arthralgia develops in 25% and arthritis in 10% after immunization with rubella-containing vaccine. There is no evidence of increased risk of new onset, chronic arthropathies or neurologic conditions.
Ig
Injection site pain and tenderness, urticaria, and angioedema may occur.
Immune Thrombocytopenic Purpura (ITP)
Rarely, ITP occurs within 6 weeks after immunization with MMR or MMRV vaccine. In most children, post-immunization thrombocytopenia resolves within three months without serious complications. In individuals who experienced ITP with the first dose of MMR or MMRV, serologic status may be evaluated to determine whether an additional dose of vaccine is needed. The potential risk to benefit ratio should be carefully evaluated before considering vaccination in such cases.
Meningococcal (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications
The Advisory Committee on Immunization Practices (ACIP) recommends vaccination against meningococcal disease for people who travel to or reside in countries where N. meningitidis is hyperendemic or epidemic, particularly if contact with the local population will be prolonged. Hyperendemic regions include the meningitis belt of Africa during the dry season (December–June). proof of receipt of quadrivalent vaccination against meningococcal disease is required for people traveling to Mecca during the annual Hajj and Umrah pilgrimages.
Routes and dosing: (IM) 0.5 mL X 1 dose
Duration of protection: When travelling to areas where meningococcal vaccine is recommended or required. Re-vaccination with Men-C-ACYW is recommended every 3 to 5 years of age for those vaccinated at 6 years of age and younger, and every 5 years for those vaccinated at 7 years of age and older. Previously vaccinated travellers are advised to check requirements for re-vaccination with meningococcal vaccines prior to travel to the Hajj as more frequent vaccination may be required (in previous 3 years) Men-C-ACYW vaccines are not authorized for use in those 56 years of age and older and 4CMenB vaccine is not authorized for use in those 17 years of age and older; however, based on limited evidence and expert opinion its use is considered appropriate.
Immunogenicity and efficacy
Vaccine effectiveness of Men-C-ACYW-DT within 3 to 4 years of vaccination in adolescence is 80% to 85%; however, effectiveness wanes over time. There is no efficacy or effectiveness data available for Men-C-ACYW-CRM, Men-C-ACYW-TT or 4CMenB. Men-C-C and Men-C-ACYW vaccines are immunogenic in infants and toddlers but those vaccinated in infancy show a waning immune response over time. Vaccination with conjugate meningococcal vaccine primes the immune system for memory and induces good anamnestic responses; however, anamnestic response may not be sufficient to prevent disease after exposure and circulating antibodies are thought to be essential. Approximately 7–10 days are required after vaccination for development of protective antibody levels
Adverse effects: For polysaccharide vaccine, the incidence of local reactions (such as pain and redness at the injection site) has ranged from 4% to 56% across studies. Severe reactions are rare, with an incidence of
Mumps (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications: Protection against mumps is especially important for people planning travel to destinations outside of North America. Travellers born in 1970 or later, who do not have documented evidence of receiving two doses of mumps-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed mumps disease should receive two doses of mumps-containing vaccine. Travellers born before 1970, who do not have documented evidence of receiving mumps-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed mumps disease, should receive one dose of MMR vaccine. Mumps is endemic in many countries.
Route and dose: (SC) 0.5mL Children (12 months to 17 years of age) Two doses of mumps-containing vaccine should be given for routine immunization of children and for immunization of children and adolescents who missed mumps immunization on the routine schedule. MMRV vaccine may be used in children aged 12 months to 12 years. Routine immunization: adults born before 1970 are generally presumed to have acquired natural immunity to mumps; however, some of these individuals may be susceptible. Adults without contraindications, born in 1970 or later who do not have documented evidence of receiving mumps-containing vaccine on or after their first birthday, or laboratory evidence of immunity, or a history of laboratory confirmed mumps infection should be immunized with one dose of MMR vaccine.
Efficacy and immunogenicity
umps vaccine effectiveness has been estimated at 62% to 91% for one dose and 76% to 95% for two doses. In clinical studies, a single injection of MMR vaccine induced measles antibodies in 95%, mumps antibodies in 96%, and rubella antibodies in 99% of previously seronegative children.
Adverse effects:
Adverse events following MMR immunization occur much less frequently and are far less severe than those associated with natural disease. Adverse reactions are less frequent after the second dose of vaccine and tend to occur only in those not protected by the first dose. Six to 23 days after MMR immunization, approximately 5% of immunized children experience malaise and fever, with or without rash, lasting up to 3 days. Parotitis, rash, lymphadenophy, and joint symptoms also occur occasionally after MMR immunization MMRV vaccine Pain and redness at the injection site, low-grade fever or both occur in 10% or more of vaccinees. Rash, including measles-like, rubella-like and varicella-like rash, as well as swelling at the injection site and moderate fever, greater than 39°C occur in 1% to less than 10% of vaccinees. As varicella-like rashes that occur within the first two weeks after immunization may be caused by wild-type virus, health care providers should obtain specimens using viral transport media from a lesion of the vaccinee to ensure that varicella disease is not confused with a reaction to vaccination. Rubella-containing vaccines Acute transient arthritis or arthralgia may occur 1 to 3 weeks after immunization with rubella-containing vaccine; it lasts for about 1 to 3 weeks, and rarely recurs. It is more common in post-pubertal females, among whom arthralgia develops in 25% and arthritis in 10% after immunization with rubella-containing vaccine. There is no evidence of increased risk of new onset, chronic arthropathies or neurologic conditions.
Pertussis (Indications/contraindications, routes of administration, dosing regimens, duration of protection, immunogenicity, efficacy, potential adverse reactions and medical management of adverse reactions)
Indications:
Unimmunized or incompletely immunized travellers should receive diphtheria-tetanus-pertussis-polio-Hib-containing vaccine as appropriate for age. adults aged ≥19 years who have not previously received Tdap should receive a single dose of Tdap instead of tetanus and diphtheria toxoids (Td) vaccine for booster immunization against tetanus, diphtheria, and pertussis. Tdap vaccine, when indicated, should be administered to adolescents and adults regardless of interval since the last dose of Td vaccine. To provide pertussis protection before travel, Tdap can be given regardless of the interval from the last Td, except to people for whom pertussis vaccination is contraindicated or for people who have previously received Tdap
Routes and dose 0.5 mL (IM) Routine pertussis immunization of infants: DTaP-IPV-Hib vaccine should be given at 2, 4, 6 and 12 to 23 months of age (generally given at 18 months of age). Adults (18 years of age and older) Adults who have not previously received Tdap vaccine in adulthood should receive one dose of Tdap vaccine, which can be administered regardless of the interval since the last dose of tetanus and diphtheria toxoid-containing vaccine.
Duration: Adults who have not previously received Tdap vaccine in adulthood, should receive one dose of Tdap vaccine, regardless of the interval since the last dose of tetanus or diphtheria toxoid-containing vaccine.
Efficacy and immunogenicity: The vaccine efficacy following the primary series with acellular pertussis vaccines is estimated to be about 85%, and approximately 90% following booster immunization. Immunologic correlates of protection against pertussis are not well-defined, but higher levels of anti-pertussis antibodies seem to be associated with greater protection. In general, acellular pertussis-containing combination vaccines have demonstrated good immunogenicity of their component antigens. Consistently high response to pertussis vaccine has been observed after booster vaccination.
Adverse effects:
Redness, swelling and pain at the injection site are the most common adverse reactions to childhood pertussis-containing combination vaccines. A nodule may be palpable at the injection site and may persist for several weeks. Abscess at the injection site has been reported, especially if care is not taken to ensure IM injection, and inadvertent SC administration occurs. Among adults given a booster dose of Tdap vaccine, very common reactions include pain, redness and swelling at the injection site, headache, and fatigue. Fever and chills are common reactions. Overall, adverse reactions are less common in adults than adolescents. The interval between the childhood DTaP vaccine series or a dose of Td vaccine, and a dose of Tdap vaccine does not affect the rate of injection site or systemic adverse events.
