Transcript Immunization Update 2015

UPDATE ON PEDIATRIC
IMMUNIZATIONS- 2016
BLAISE L. CONGENI M.D.
BLAISE L. CONGENI M.D.
DIRECTOR, INFECTIOUS DISEASES
AKRON CHILDREN’S HOSPITAL
Threats to Vaccines
• Falling rates
• Success of past vaccines
–Lack of awareness of disease
that is prevented
• Effects of anti-vacccine
movement
–Fear, mistrust, ignorance
GA Poland 2011
Vaccines: Very high benefit/risk ratio
 All vaccines have possible side effects, most
mild, rarely severe
 The risk of disease far outweighs the risk of
vaccine
 MESSAGE:
 Vaccines Effective
 Safe
 Need to recommend
Impact of Vaccines

Vaccines are one of the most
important tools we have to protect the
health of our nation's most vulnerable
citizens, our children. (also adults,
especially older adults)
 In last 100 years life span of
Americans has doubled; largely as a
result of vaccines and sanitation
GA Poland 2011
Need to improve Vaccine
Uptake
• Clear and unambiguous message
to public, patients, providers
– High benefit/risk ratio
– SAFE
• Low rates lead to outbreaks and
death
• Anti-vaccine movement is harmful
to public health
GA Poland 2011
The Communications Breakdown
Recommendation
“You
need to
get this
vaccine.”
OR
“I want
you to
get this
vaccine.”
VaccineMotivated
Patient
Not a Recommendation
“Do you
want this
vaccine?”
OR
“Think
about
getting the
vaccine.”
VaccineAmbivalent
Patient
Physician-Patient
Miscommunication
National Foundation for Infecgious Diseases. Surveys of consumers and physicians
2010
Burden of Vaccine-Adult Preventable
Disease in the US
Disease
Annual Burden of Disease, United States
Influenza
200,000 hospitalizations; 36,000 deaths (> 90% in older
adults)
Invasive
pneumococcal
disease
44,000 cases, 4500 deaths (higher rates of both in older
adults and persons with comorbidities)
Hepatitis B
51,000 infections (95% adults); 2000-3000 deaths;
1.25 million with chronic HBV infection
Human
papillomavirus
6.2 million new infections (>4000 women die in US
annually; ? Male deaths)
Pertussis
10,454 cases reported in 2007 (3152 adults)
Severe illness in infants; often transmitted by older child or
adult
Zoster
1 million cases; risk for shingles and postherpetic neuralgia
increases with age
CURRENT RECOMMENDATIONS FOR
HPV VACCINATION IN THE UNITED
STATES
• Routine vaccination at age 11 or 12 years*, HPV9,
HPV4, or HPV 2-females. Only HPV9 or HPV4 males.
• Vaccination recommended through age 26 for
females and through age 26 for males not
previously vaccinated
• Vaccination recommended for
immunocompromised persons (including persons
HIV-infected) and for men who have sex with men
through age 26
• 3-dose schedule (0,1-2 (prefer 2 months,)and 6
months)
• Revaccination not routinely recommended.
*The vaccination series can be started at age 9 years
NEW DOSING GUIDELINES
FDA 10/7/16
• HPV 9 can be administered to adolescents 9-14,
before 15th birthday, finish before age 16, with either
a 2 or 3 dose schedule.
• The second dose should be administered 6-12
months after the first dose.
• If the second dose is administered less than 5
months after the first dose, a third dose should be
given at least 4 months after the second dose.
ACIP RECOMMENDATIONS FOR HPV
VACCINATION
• Females:HPV2, HPV4, HPV9
• Routine: 11 or 12 year olds
• Catch Up: 13-26 year olds
• Males:HPV4, HPV9
• Routine: 11 or 12 year olds
• Catch Up: 13-21 year olds
Vaccination can be started as early as age 9 year old
MMWR 2015, 64:300-304
AVAILABLE HPV VACCINES
Bivalent (HPV 2)
Quadrivalent
(HPV 2)
9-valent (HPV 9)
Manufacturer
GlaxoSmithKline
Merck
Merck
L1 VLP types
16,18
5,11,16,18
5,11,16,18,31,33,45,
52,58
Adjuvant
ASO4:
500 g aluminum
hydroxide
50 g 3-0–desacyl-4’monophosphoryl lipid
A
AAHS:
225 g amorphous
aluminum
hydroxyphosphate
sulfate
AAHS:
500 g amorphous
aluminum
hydroxyphosphate
sulfate
Licensed
Females 9-25 years
Females 9-26 years
Males 9-26 years
Females 9-26 years
Males 9-26 years
L1 – Major capsid protein; VLP – virus like particle
9-VALENT HPV VACCINE (9VHPV)
• Licensed by FDA December 10, 2014
• Females 9-26 yrs, males 9-15 yrs
• Trails conducted with 3-dose schedule
• L1 VLP vaccine, similar to quadrivalent HPV vaccine
• Targets 5 additional high risk types
• 6,11,16,18,31,33,45,52,58
• Males 16-26 yrs – not part BLA submitted in 2013
• Data presented to ACIP October 2014
• sBLA submitted to FDA
BLA –Biologics License Application
BURDEN OF HPV DISEASE AND
POTENTIAL IMPACT OF 9 VALENT
VACCINE
4 HPV types cause:
(6, 11, 16, and 18)
9 HPV types cause a
total of:
(6, 11, 16, 18, 31, 33, 45,
52, and 58)
Cervical cancer cases
70%1
90%1
Vulvar cancer casesa
75%2
90%2
Vaginal cancer casesa
65%3
85%3
Anal cancer casesa
85%4
90%–95%4
High-grade cervical
precancersa,b
50%5
80%5
Low-grade cervical lesionsa
25%5
50%5
Genital warts cases
90%6
90%6
Estimated type contribution for
certain HPV-related cancer
and disease cases
HPV-9, FAQ
• 14% of HPV associated cancers in females, and 4% of
HPV cancers in males are caused by the additional
types in HPV 9.
• If a series was started with HPV4 or HPV2, can it be
completed with HPV9? Yes.
• Is additional vaccination recommended for one who
has completed HPV2/4 series? No recommendation is
made for additional doses of HPV 9.
• If a person desires additional protection following
completion of HPV2/4, what are the issues? Safety v
efficacy.
• Cost per QALY-additional $100,000/yr. In contrast, routine HPV9
is cost saving.
ACIP July 2015, Supplemental Information and Guidance
HPV VACCINE COVERAGE RATES
Percent Vaccinated (%)
100
80
Tdap
60
MCV4
HPV-1 Females
HPV-3 Females
40
HPV-1 Males
HPV-3 Males
20
0
2007
2008
2009
2010
MMWR 2008, 57:1100-1103
2011
2012
2013
2014
IMPACT OF MISSED OPPORTUNITIES
FEMALES, ≥ 1 DOSE HPV, CDC
ANALYSIS
100
91.3
Percent
80
60
40
20
0
MMWR 2014, 63:613
48.6
Potential
coverage
Options For Meningococcus B
Immunization 10-25 Years Old
• Immunize all high risk patients. Sickle
cell, complement defects, occupational.
• Discuss increased risk with parents as
patients leave for school, and offer.
• Routinely immunize.
ACIP RECOMMENDATIONS FOR USE OF
MENINGOCOCCAL B VACCINES
• The committee voted 14-1 to recommend the
serogroup B vaccines be made available to people
ages 16-23 years to provide short term protection
against most strains.* The majority agreed 16-18 is
the preferred age range so that the protection will
last into the highest risk period.
• Instead of making the vaccine routine for young
adults, the group deemed it a category B
recommendation, meaning doctors and patients
will decide on an individual basis whether to use it.
• 2 v 3 dose schedule. Relationship to dose timing,
1v6 mo, presence of outbreak, immune status of
patient.
*June 24, 2015 ACIP
Adolescent and Adult
Pertussis Vaccination
• Primary objective
– protection from pertussis
• Secondary objective
– reduce reservoir of Bordetella pertussis
– potentially reduce incidence of pertussis in other
age groups and settings
2013- “No routine booster Tdap” at 21 years of age,
as it would only have a modest effect on cases of
pertussis. (3% reduction expected)*
*AAP News Vol 34 No 8, August 1 2013
Positive
Culture
Diagnostic Laboratory Findings in
Pertussis
Catarrhal
Paroxysmal
Convalescent
Lymphocyte Count
(thousands)
Stage
5
0
3
0
1
0
1-2
2-5
5-12+
Time After Onset of Symptoms (weeks)
Adapted from Mortimer EA. In: Krugman’s Infectious Diseases of Children. 10th ed. Mosby Year Book, Inc; 1998:335-313.
Antigenic Components of
B pertussis
FIM
FHA
PT
• Pertussis toxin (PT), also known
as “lymphocytosis-promoting factor,”
secreted (systemic action)
• Filamentous hemagglutinin (FHA)
• Pertactin (PRN) or 69 kD* protein
PRN
• Fimbrial agglutinogens (FIM)
(1-4 serotypes)
*kD = kilodalton.
Edwards KM et al. In: Plotkin SA et al, eds. Vaccines. 1999;293-344.
Epidemic Pertussis and Acellular
Pertussis Vaccine Failure in the 21st
Century
• The two greatest contributors to the resurgence of
pertussis are greater awareness and more sensitive
diagnosis. (routine use of PCR)
• Other factors include: decay in antibody, Th1/Th2 v
Th1/Th17 response, linked epitope suppression,
incorrect balance of antigens, and pertactin-deficient
strains of B. pertussis.
• “Of most importance is to see that pregnant women
receive Tdap with each pregnancy.”
– Could prevent all infant deaths, other option would be
to change the schedule.
Cherry, JD Peds. 2015;135:1130-1131.
Pertussis Outbreaks 2013
• Impact of diagnosis utilizing new and “highly
sensitive” methodologies, ie. PCR
• Virulence and emergence of pertactin-negative
strains of B. pertussis
• Routine immunization with Tdap for all pregnant
women “irrespective of the patient’s prior history
of receiving Tdap.”
– Optimal timing 27-37 weeks of gestation
– If not administered during pregnancy, give dose
immediately postpartum
ASSOCIATIONS OF VACCINATION STATUS WITH
CLINICAL OUTCOMES, MULTIPLE LOGISTIC
REGRESSION ANALYSIS – PORTLAND, OREGON,
METROPOLITAN AREA, 2010-2012 (N=624)
Outcome
Vaccinated
OR
(95%Cl)
612
12
73.5
25.0
Referent
0.1 (.0-.4)
0.2 (.1-.8)
605
19
73.1
57.9
Referent
0.6 (.21.3)
0.6 (.21.6)
No.
Hospitalized
No
Yes
Positive radiograph for
pneumonia
No
Yes
AgeAdjusted
OR (95%
Cl)
% Ever
Severe Illness a
No
593
73.9
Referent
Yes
31
48.4
1.3 (.2-.7)
Abbreviations: Cl, confidence interval; OR, odds ratio.
a. Illness that resulted in hospitalization, pneumonia, acute
encephalopathy, or seizures.
0.4 (.2-.9)
Odds Ratios for Pertussis Disease Associated with Receipt of 5 DTaP Doses and
Estimated Vaccine Effectiveness for Each Year Following the Complete DTaP Series
Primary Analysis a
Estimated VE Model
Cases No.
(n=682)
Controls, No.
(n=2016)
OR (95% Cl)
Estimated VE,
% (95% Cl)
Overall No. of doses
0
5
53
629
19
1997
1(Reference)
0.11(0.06-0.21)
1 (Reference)
88.7(79.4-93.8)
Time since 5th dose, mo
0 doses
<12
12-23
24-35
36-47
48-59
≥60
53
19
51
79
108
141
231
19
354
391
366
304
294
288
1(Reference)
0.02(0.01-0.04)
0.05(0.02-0.09)
0.08(0.04-0.13)
0.13(0.07-0.24)
0.17(0.09-0.31)
0.29(0.15-0.54)
1(Reference)
98.1(96.1-99.1)
95.3(91.2-97.5)
92.3(86.6-95.5)
87.3(76.2-93.2)
82.8(68.7-90.6)
71.2(45.8-84.8)
Abbreviations: IE, Interval estimate, OR, odds ratio; VE, vaccine effectiveness.
a ORs and estimated VE, accounting for clustering by county and clinic
Patient DS
• First admission for this 15 yo WM who presents with 3 day
H/O trismus, back and abdominal muscle spasms.
• In the last 24 hours symptoms have progressed to point of
making it difficult to breathe.
• Labs: WBC-13100 with 82% neutrophils, CXR-nl, neck
CT-reactive lymphadenopathy.
• Pe: alert, responsive, oriented x3. Severe cytic acne, cuts
and abrasions to great toe and right wrist.
Patient DS
• Patient was started on metronidazole, given a dose of
Tdap, TIG, diazepam, and NSAID as well as fluids.
• Improvement was very slow but he was transferred out of
ICU in 5 days, during which time he developed significant
ptosis.