Vaccinations

Thi Mai, Julia Lee, Kim Truoung, Melvie Kim, Maylyn Martinez, Cory

Taylor

Influenza Vaccine• INDICATIONS

– Everyone older than 6 months– Prior to 2010, used to be only at risk individuals and their close contacts

• WHY DO I NEED IT, DOC?– Influenza vaccination not only reduces the risk of influenza infection but also reduces

the severity of illness in those who are infected -- PMID 23532475, Clin Infect Dis 2012– Vaccination results in fewer influenza infections and fewer missed days from work in

such individuals -- PMID 10411194, JAMA 1999

• HOW DO THEY PICK THE ANTIGENS?– Global surveillance of influenza viruses circulating at the end of the prior influenza

season– Quadrivalent means two influenza A virus es and two influenza viruses– Translates in a large committee, a large dart board, and a lot of darts

Influenza Vaccine -- Preparations• STANDARD DOSE TRIVALENT OR QUADRIVALENT INACTIVATED

– intramuscular vs jet-injected– any age

• HIGH DOSE TRIVALENT INACTIVATED– intramuscular– greater than 65 years old– may be more effective in individuals on statin– may be displaced in future by forthcoming adjuvinated standard dose

• INTRADERMAL TRIVALENT OR QUADRIVALENT INACTIVATED– 1/5 the dose = more vaccine to go around– higher incidence of site reactions: erythema, swelling, pruritis, but not pain or sore shoulder

• STANDARD DOSE QUADRIVALENT LAIV– intranasal– non-pregnant adults younger than 50– contraindicated for immunocompromised or close contacts

• FOR EGG ALLERGIES: TRIVALENT CELL-CULTURED vs TRIVALENT RECOMBINANT

Influenza Vaccine – Schedule

• Northern Hemisphere – October - March• Southern Hemisphere – May - August• Tropics and Cruise ships: year-round

Influenza Vaccine -- Shortages

• Limited supply of vaccine may necessitate rationing• Higher risk individuals and contacts:

– Extremes of Age: younger than 2, older than 65– Lung, heart, liver, kidney failure; diabetes; severely

debilitated– Healthcare workers– Pregnant and postpartum– Health and custodial care facility residents– Immunocompromised

Tetanus, Diptheria, Pertussis

• DTaP series in children until 4-6 years old– Start at 6 weeks; 4-5 doses depending on timing

• Tdap booster 10 years later• Td booster every 10 years for life

– Tdap booster again if older than 19 replacing routine Td • If unsure or less than 3 Td prior, start series of 3

similar to DTaP schedule; at least one should be Tdap

• Pregnant – you get Tdapped each pregnancy

PNEUMOCOCCAL VACCINES

Pneumococcal Disease• Second most common cause of vaccine preventable

death in the US• Major clinical syndromes include

• Pneumonia• Bacteremia• Meningitis

.

It is better to prevent than to try and fight pneumococcal disease with antibiotics that might not work.

Available Vaccines• >90 different capsular serotypes identified, however not

possible to include all in a vaccine• Available vaccines contain capsular serotypes found to

cause invasive disease:

1) Pneumococcal polysaccharide vaccine (Pneumovax, PPSV23)

2) Pneumococcal conjugated vaccine (was Prevnar 7, PCV7, now replaced by Prevnar 13, PCV13)

Pneumovax (PPSV23)• Consists of capsular material from 23 serotypes• These serotypes cause about 50-60% of pneumococcal

disease in adults• Has been used in adults for decades, but not in infants

since polysaccharide antigens are poorly immunogenic in such individuals

Updates on Prevnar (PCV7 13)• Consists of capsular material from 13 serotypes,

covalently linked to a protein almost identical to diphtheria toxin• This link renders vaccine immunogenic to infants and toddlers

• Timeline:• 2000 - Prevnar 7 was adopted was adopted for universal use in

toddlers/infants• 2010 – Prevnar 13 recommended in its place• 2012 – Prevnar 13 also recommended for use in selected high risk

adults• 2014 – Prevnar 13 also recommended for use in adults > 65

Adult 65 and Older• CDC recommends all adult ≥ 65 receive 2 types of

pneumococcal vaccines• One dose of PCV13 (first)• One dose of PPSV23 ( 6 to 12 months after PCV vaccine)• This age group requires both vaccines for the best protection

against pneumococcal disease

Adult 19 to 64 Years Who Only Need PPSV23

• Those with chronic conditions• Asthma• Diabetes• Heart disease• Alcoholism• Liver disease

• Cigarette smokers• Residents of nursing homes or other long-term care

facilities• When they turn 65 this group should receive a dose of

PCV13

Adults 19 to 64 Who Should Receive both PCV13 and PPSV23*• Functional or anatomic asplenia†• Cochlear implants • Cerebrospinal fluid leaks†• Lymphoma, leukemia, Hodgkin disease,†• Solid organ transplants†

• * PCV13 and PPSV23 cannot be given at the same visit• † A second PPSV23 vaccine is recommended for these

individuals five years after the first PPSV23 dose

Herpes Zoster (Shingles) Vaccine

Herpes Zoster (shingles)• Caused by reactivation of a latent varicella zoster virus infection

• Generally associated with normal aging and with anything that causes reduced immunocompetence

• Lifetime risk of 32% in the United States• Estimated 1 million cases zoster diagnosed annually in the U.S.

Herpes Zoster Vaccine(Zostavax)

• Contains live attenuated varicella virus in an amount that is approximately 14 times greater than that in regular varicella vaccine

• Approved for persons 60 years of age and older• Administered by the subcutaneous route

Zostavax Clinical Trial• Compared to the placebo group the vaccine group had:

• 51% fewer episodes of zoster• less severe disease• 66% less postherpetic neuralgia

• No significant safety issues were identified

NEJM 2005;352(22):2271-84.

Recommendations for Zoster Vaccine

• Single dose of zoster vaccine for adults 60 years of age and older whether or not they report a prior episode of shingles

• Persons with a chronic medical condition may be vaccinated unless a contraindication or precaution exists for their condition

MMWR 2008;57(RR-5)

Zoster Vaccine Contraindications• Severe allergic reaction to a vaccine component or

following a prior dose• Pregnancy or planned pregnancy within 4 weeks• Immunosuppression

MMWR 2008;57(RR-5)

Zoster Vaccine ContraindicationsImmunosuppression

• Leukemia, lymphoma or other malignant neoplasm affecting the bone marrow or lymphatic system• persons whose leukemia or lymphoma is in remission and who have not received chemotherapy or radiation for at least 3 months can be vaccinated

• AIDS or other clinical manifestation of HIV infection• includes persons with CD4+ T-lymphocyte values less than 200 per mm3 or less than 15% of total lymphocytesMMWR 2008;57(RR-5)

Zoster Vaccine ContraindicationsImmunosuppression

• High-dose corticosteroid therapy • 20 milligrams or more per day of prednisone or equivalent lasting

2 or more weeks• vaccination should be deferred for at least 1 month after

discontinuation of therapy

MMWR 2008;57(RR-5)

HEPATITIS A• Hepatitis A is a form of acute viral hepatitis • Symptoms include acute onset jaundice, scleral icterus, abdominal pain, flu-like symptoms, anorexia, nausea,

diarrhea• Transmission: fecal-oral route often via contaminated food or water

• Vaccine recommendations: – Everyone, but especially those at higher risk– Can start as early as 1 years old

• Higher risk groups:– Living or traveling to endemic areas with hepatitis A

• Central or South America, Mexico, Asia (except Japan), Africa, and eastern Europe• At least 1 month before traveling

– Men who have sex with men– Chronic liver disease– Those who have close contact with international adoptees from endemic region– Postexposure prophylaxis in those with sick contacts– Patients who are treated with clotting factor concentrates (ie for hemophilia)

• Schedule: at month 0 and 6-12 – Inactivated virus, and usually combined with Hepatitis B (TWINRIX), although there are single antigen Hep A

vaccines (HAVRIX, VAQTA)

HEPATITIS B

• Hepatitis B virus can cause acute and chronic liver disease– Acute: manifestations range among subclinical, icteric,

and fulminant hepatitis– Chronic: can progress from asymptomatic carrier to

chronic hepatitis to cirrhosis with increased risk for hepatocellular carcinoma

• Worldwide, 240 million are chronic carriers and over 780,000 hepatitis B related deaths occur annually

Hepatitis BRecommendations for vaccine• All infants, beginning at birth and then all unvaccinated children <19 years

• High risk individuals– Sexual partners of HBsAg-positive persons– Sexually promiscuous individuals at risk for STDs in general– Injection drug users

• Other individuals to think about– Susceptible household contacts of HBsAg-positive persons– Healthcare and public safety workers with occupational exposure to blood– Screen women at their first prenatal visit– Chronic liver disease or HIV– Persons with ESRD regardless of dialysis status– Travelers to endemic HBV regions– Unvaccinated adults with diabetes mellitus age 19-59 years – Age >60 is at discretion of clinician– Patients who request it

Hepatitis B• Schedule = 3 shots

– Children: at birth, then 1-2 months, then 6-18 months old– Adults:

• At months 0, 1, and 4-6 months for single antigen vaccine ENGERIX and RECOMBIVAX HB• At month 0, 1, and 6 for combined HepAHepB vaccine TWINRIX

• Incomplete vaccinations: not necessary to restart entire series– If stopped after first dose, second dose should be given asap, then third dose after 8 weeks– If stopped after 2nd dose, third dose should be give as soon as possible

• Contraindications and Adverse reactions– Contraindications: serious allergic reaction to a prior dose of hepatitis B vaccine, a

component of the hepatitis B vaccine, or yeast – Common adverse reactions: soreness at site, low grade fever, malaise, headache, joint pain

and myalgia

Hepatitis B• Post-vaccination testing

– current hepatitis B vaccines have a response rate of 95 percent and immune response can last over 20 years

– No indication to test for seroconversion (Hep B surface antibody), except:

• health-care workers• patients on chronic hemodialysis• individuals (such as spouses or sexual partners of carriers and infants of

carrier mothers) who are at risk for recurrent exposure to hepatitis B– Draw HBsAb 1-2 months after completion of vaccination series – Nonresponders should complete a second three-dose vaccine series,

then repeat testing• Non-responders to the second course of vaccine should be tested for HBsAg.

HUMAN PAPILLOMA VIRUS• HPV can cause several types of cancer

– cervical, anal, oropharyngeal– Type 16, 18 cause 70% of cervical cancers

• HPV vaccines: GARDASIL, CERVARIX– Both protect against HPV type 16 and 18– Gardasil also prevents against HPV type 6 and 11

• Gardasil 9 protects against additional 5 high risk strains– Cervarix is approved for females 9-25 years old– Evidence of cross-protection against a few additional HPV

types that can cause cancer

HPV VACCINE

Recommendations: 3 shots• Boys and girls starting at age 11 or 12• Male until 21• Female until age 26• High risk males until age 26:

– MSM– immunocompromised

Schedule: vaccinate at months 0, 1-2, and 6

Question 1

• A 63-year-old man is in clinic for routine follow up. His recently diagnosed COPD is controlled with tiotropium and albuterol as needed. He receives yearly influenza vaccinations. Although he has never received the pneumococcal vaccination, all other immunizations are up-to-date.

• On physical examination, vital signs are normal and lungs are clear to auscultation.

• Which of the following is the best influenza and pneumococcal immunization regimen for this patient?

A: Influenza vaccine nowB: Influenza and pneumococcal vaccines nowC: Influenza vaccine now and pneumococcal vaccine at the next routine visitD: Influenza vaccine now and pneumococcal vaccine at age 65 years

• Which of the following is the best influenza and pneumococcal immunization regimen for this patient?

A: Influenza vaccine nowB: Influenza and pneumococcal vaccines nowC: Influenza vaccine now and pneumococcal vaccine at the next routine visitD: Influenza vaccine now and pneumococcal vaccine at age 65 years

• The most appropriate immunization regimen for this patient is influenza and pneumococcal vaccines now.

• Pneumococcal vaccine may be administered concurrently with other vaccines, such as the influenza vaccine, but at a separate site. Waiting for the next scheduled routine visit to administer the pneumococcal vaccine carries a risk of not administering the vaccine in a timely fashion and the possibility of failing to administer the vaccine at all.

• Influenza and pneumococcal vaccines are recommended for patients with COPD.

• Influenza vaccine is recommended annually for all adults. High-dose influenza vaccine is an option for patients 65 years and older.

• Pneumococcal vaccine is recommended for adults 65 years and older. Pneumococcal vaccine is recommended for all adults regardless of age if they have the following chronic conditions: chronic lung disease (including asthma), chronic liver disease, diabetes mellitus, cirrhosis, chronic alcoholism, functional or anatomic asplenia, immunocompromising conditions (including chronic kidney failure or the nephrotic syndrome), cochlear implants, or cerebrospinal fluid leaks. Other indications are smokers and residents of nursing homes or long-term care facilities.

• One-time revaccination is indicated after 5 years for persons aged 19 to 64 years with the nephrotic syndrome or chronic kidney failure, functional or anatomic asplenia, and immunocompromising conditions. One-time revaccination is recommended for patients who were vaccinated 5 or more years ago and were less than 65 years of age at the time of primary vaccination. The 7-valent pneumococcal polysaccharide vaccine seems to induce a superior immune response than the 23-valent-pneumococcal polysaccharide vaccine. Data suggest that influenza vaccination, but not pneumococcal vaccination, is associated with reduced all-cause mortality.

Key Point

• Influenza and pneumococcal vaccines are recommended for patients with COPD and can be administered at the same time but at different sites.

Uptodate.com

Question 2

• A 30-year-old woman is evaluated during a routine examination. She was born in the United States and reports getting “routine shots” in childhood. She received a routine tetanus, diphtheria, and acellular pertussis (Tdap) booster 5 years ago. She is sexually active with a single lifetime sexual partner. She has had no history of sexually transmitted infection. She has had regular Pap smears without any abnormal results; her most recent was 3 years ago. She does not smoke cigarettes. She works as a 3rd-grade school teacher. Physical exam is normal.

• Which of the following vaccinations should be administered?

A: Hepatitis B vaccine seriesB: Human papillomavirus vaccine seriesC: Influenza vaccineD: Tetanus and diphtheria (Td) vaccine

• Which of the following vaccinations should be administered?

A: Hepatitis B vaccine seriesB: Human papillomavirus vaccine seriesC: Influenza vaccineD: Tetanus and diphtheria (Td) vaccine

• This healthy 30-year-old woman should receive a seasonal influenza vaccination. The Centers for Disease Control and Prevention currently recommends that all adults be vaccinated annually against influenza, regardless of risk factors. Vaccination usually takes place between September and March in the Northern hemisphere. Healthy adults can be vaccinated with either an inactivated vaccine injected intramuscularly or a live attenuated intranasal vaccine.

• The hepatitis B vaccine is indicated for all children and adolescents through age 18 years, persons with HIV or other recent sexually transmitted infections, persons who are sexually active but not monogamous, workers with occupational exposure to blood, clients and staff of institutions for the developmentally disabled, correctional facility inmates, illicit drug users, persons with diabetes mellitus who are younger than 60 years, and persons with advanced chronic kidney disease who are approaching hemodialysis. Hepatitis B vaccination is also indicated for those planning travel to an endemic area and those with an increased risk for morbidity related to the disease, as well as for persons who request vaccination. This patient has no indication for hepatitis B vaccination.

• The human papillomavirus vaccine is licensed for males and females aged 9 through 26 years and is recommended for females between the ages of 11 and 26 years and males between the ages of 11 and 21 years. The vaccine is not indicated for this 30-year-old woman

• Current recommendations are that a tetanus and diphtheria (Td) vaccine be routinely administered every 10 years.

• Owing to an increased incidence of pertussis, thought in part to be related to waning immunity from childhood vaccination, all adults are recommended to receive a single tetanus, diphtheria, and acellular pertussis (Tdap) vaccination regardless of the interval since their last Td booster (although it may be given in place of a decennial Td booster if scheduled); this is a particularly important recommendation for persons aged 65 years or older because of the high burden of associated disease in this patient population.

• In addition, all postpartum women, health care workers, and adults who have close contact with infants younger than 12 months should receive a one-time Tdap booster if not already given. This patient is not due for a routine repeat Td booster for another 5 years and has no indications to receive either a Td or Tdap vaccination at this time.

Key Point

• Annual seasonal influenza vaccination is recommended for all adults, regardless of risk factors.

Question 3

• A 58-year-old man is in clinic to establish care. A review of his previous records shows he received a pneumococcal vaccination 6 years ago when he was admitted to the hospital with community-acquired pneumonia. He has no complaints and feels well. Medical history includes type 2 diabetes mellitus, hypertension, and hyperlipidemia. Medications include insulin glargine, metformin, lisinopril, and simvastatin. His physical exam is unremarkable.

• When should this patient receive an additional pneumococcal vaccination?

A: TodayB: Today and repeat every 5 yearsC: Today and at age 65 yearsD: At age 65 yearsE: No further pneumococcal vaccinations are required

• When should this patient receive an additional pneumococcal vaccination?

A: TodayB: Today and repeat every 5 yearsC: Today and at age 65 yearsD: At age 65 yearsE: No further pneumococcal vaccinations are required

• This man should receive a single pneumococcal polysaccharide vaccination at age 65 years.

• Adults 65 years and older should be immunized against pneumococcal pneumonia.

• The vaccine contains 23 antigen types of Streptococcus pneumoniae and protects against 60% of bacteremic disease.

• Currently, immunocompetent persons vaccinated after age 65 years are not recommended to receive a booster.

• Immunocompetent persons vaccinated before age 65 years, such as this patient, should receive a single booster vaccination at age 65 years, or 5 years after their first vaccination if they were vaccinated between the ages of 60 and 64 years.

• The vaccine is also recommended in some populations of younger patients, including:

– Alaskan natives and certain American Indian populations; – residents of long-term care facilities; – patients who are undergoing radiation therapy or are on immunosuppressive

medication; – patients who smoke; and patients with chronic pulmonary disorders (including asthma),

diabetes mellitus, cardiovascular disease, chronic liver or kidney disease, cochlear implants, asplenia, immune disorders, or malignancies.

• There is no information on vaccine safety during pregnancy. The vaccine is reasonably effective, with high levels of antibody typically found for at least 5 years.

• Immunocompromised patients (including those with HIV infection and kidney disease) as well as patients with asplenia should receive a single pneumococcal vaccine booster 5 years after their first vaccine. This strategy would be inappropriate for this patient.

• Current recommendations do not support more than a single booster after initial pneumococcal vaccination for any persons. Hence, a strategy of vaccination every 5 years would be inappropriate.

• All patients vaccinated before age 65 years need a booster at some point. Hence, withholding further pneumococcal vaccination is inappropriate.

Key Point

• Immunocompetent persons who received the pneumococcal polysaccharide vaccine before age 65 years should receive a single booster vaccination at age 65 years, or 5 years after their first vaccination if they were vaccinated between the ages of 60 and 64 years.

Question 4

• A 24-year-old woman is evaluated during a routine examination in November. She has ulcerative colitis, which was diagnosed 10 years ago. Her last menstrual period was 5 weeks ago. She currently takes 6-mercaptopurine.

• On physical examination, vital signs are normal. Abdominal examination is normal.

• Laboratory studies, including a complete blood count, liver chemistry studies, and C-reactive protein, are normal. Pregnancy test is negative.

• Which of the following vaccinations is contraindicated for this patient?

A: Hepatitis BB: Human papillomavirusC: Pneumococcal polysaccharide vaccineD: Trivalent inactivated influenzaE: Varicella (chickenpox)

• Which of the following vaccinations is contraindicated for this patient?

A: Hepatitis BB: Human papillomavirusC: Pneumococcal polysaccharide vaccineD: Trivalent inactivated influenzaE: Varicella (chickenpox)

• Varicella vaccination is contraindicated in this patient. Varicella vaccine is a live-virus vaccine; live-virus vaccines are generally contraindicated for immunocompromised patients.

• Other live vaccines include yellow fever, intranasal influenza, measles-mumps-rubella, bacillus Calmette-Guérin, and oral typhoid.

• Patients with inflammatory bowel disease (IBD) are considered immunosuppressed if they have significant protein-calorie malnutrition or are receiving corticosteroids (equivalent of prednisone 20 mg/d or higher); effective doses of 6-mercaptopurine, azathioprine, or methotrexate; anti-tumor necrosis factor (anti-TNF) therapy; or natalizumab.

• If patients have not had varicella infection or vaccination, they should ideally be vaccinated before initiating immunosuppression.

• Reactivation of hepatitis B has been reported during treatment with anti-TNF therapy, so patients should be offered hepatitis B vaccination if they are not already immune.

• Women with IBD between the ages of 9 and 26 years should be offered vaccination for human papillomavirus (HPV), because immunosuppressed patients appear to be at higher risk for HPV infection and abnormal Pap smears.

• Pneumococcal vaccination is recommended for all immunosuppressed patients with a single revaccination if 5 or more years have passed since the first dose.

• Trivalent inactivated influenza vaccination is recommended annually. • Pneumococcal, inactivated influenza, HPV, and hepatitis B vaccinations have

been shown to be safe and effective in immunosuppressed patients with IBD.

Key Point

• Live-virus vaccines such as varicella are generally contraindicated for immunocompromised patients with inflammatory bowel disease.