Adult Immunization: 2013 Update Robert H. Hopkins, Jr., MD, FACP, FAAP Professor of Internal Medicine and Pediatrics Director, Division of General Internal.

Adult Immunization:

2013 Update

Robert H. Hopkins, Jr., MD, FACP, FAAPProfessor of Internal Medicine and Pediatrics

Director, Division of General Internal MedicineDirector, Internal Medicine-Pediatrics Residency

UAMS College of Medicine

Opportunity and Reward

Immunization rates are far below goal levels

Commonly identified measure of quality preventive care

Many elements in process which can be ‘attacked’ to make improvements

Front desk

Nursing/MA

Physician

Checkout

Improvement can result in better health for your patients!

Adult Vaccination Rates= POOR!

Population Vaccine

Influenza [2011-12 season=NFS 2012] 45.5% (All adults) (Hisp 38.8%, White 49.1%, Black 35.6%, Other 40.3%)

[All] 18-49 years 35.8%

[All] 50-64 years 51.0%

> 65 years 70.8%

HCW [19-64 years] 52.9 %

PPS-23

High risk 19-49 years 20.1 %

> 65 years 62.3 %

Tetanus/Tdap [19-49 years Td, 19-64 years Tdap] 64.5 %, 12.5%

Shingles [Zoster] age 60+ 15.8 %

Hepatitis B Vaccine [19-49 years, 19-59 years+DM]

35.9 %, 26.9%

HPV Vaccine [women, men (19-26 years)] 29.5 %, 2.1%

Data: , NFS 2012, NHIS 2011

http://www.cdc.gov/flu/professionals/vaccination/nfs-survey-march2012.htm

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6204a2.htm?s_cid=mm6204a2_e

Goals: 2013 AI Update Review current ACIP Adult Immunization

recommendations

Office/Clinic Practice

Hospital Practice

Healthcare Workers

Quality improvement re: VPD

No discussion of therapeutic and other vaccines

2013 Adult Schedule [Age-Based]

2013 Adult Schedule [Disease/Indication Based]

Patients: Office and Hospital

“Universals” Influenza

Pneumococcal [PPS23]

Tdap

Zoster

“Selectives”

Pneumococcal [PCV13]

Meningococcal

Hepatitis A

Hepatitis B

HPV [HPV4, HPV2]

Women

Men

MMR

Varicella

Influenza Influenza: Orthomyxoviridae family [enveloped RNA virus]

3 types based on surface Ag [HA, NA] + internal structure A: Multiple hosts- Birds, Mammals [Man]. Many HA , NA types

‘Highly Pathogenic’ and ‘Mild’ strains

B: Human host. 1 HA and 1 NA

C: Human host. Mild illness ‘URI’

30-50K deaths annually in US from Influenza

200K+ assoc. hospitalizations, chronic illnesses exacerbations

> 90% seasonal influenza morbidity/mortality in persons > 65 years

Vaccination is most effective intervention to reduce illness and death..

Multiple vaccines avail. in US

Effectiveness variable from year/year, different patient groupshttp://www.cdc.gov/flu/avian/gen-info/flu-viruses.htm

US Influenza Vaccines IIV: =‘Inactivated’ and replaces ‘TIV’, IM admin. “All comers” 6 mo.+

Multiple vaccines varied indications [age, etc.]. 2013-14 most Trivalent--Limited supply of quadrivalent inactivated vaccine expected to be available

Intradermal IIV [Approved May 2011 for 18-64 years--smaller needle]

High-Dose IIV for 65+ population# [first avail 2010-11]

Same production as TIV, higher Ag content ~~ More local reactions

Phase 3 trials: Seroconversion, seroprotection rates > TIV for A,B strains

‘Real world’ efficacy data not yet published

New Cell culture vaccine approved 2013- option in egg-allergic [2013-14]

New Recombinant HA Vaccine approved 2013- higher HA content, no NA

LAIV: Live-attenuated, cold-adapted nasal. Quadrivalent [2A2B] 2013-14 Indicated only for healthy people 2-49 yrs.

# Falsey, et.al. J ID 2009, June9 [Epub]; C. Bridges CDC Personal Comm. 3/2013

InfluenzaVaccine changes annually, recommend yearly vaccination!

Vaccine production: ~9 months

Egg-based [all but new recombinant HA, cell-culture vaccines]

Strain choice (Feb) reflects antigenic drift [Prior season + S. Hemisphere]

US Vaccination season: Vaccine avail. to ‘disease passed’…[Sept-April?]

Predominant strain types [Dz and Vax] since 1977: A H1N1, A H3N2, B

2012-13 Vaccine strains:

Influenza A/California/7/09 (H1N1)-like virus [Since 2009 Pandemic]

Influenza A/Victoria/361/2011 (H3N2)-like virus

Influenza B/Wisconsin/1/2010-like virus (B/Yamagata lineage).

2/3 strains changed from 2011-12, likely at least B will change for 2013-14

http://www.cdc.gov/vaccines/recs/acip/downloads/mtg-slides-feb09/04-1-flu.pdf

Influenza Vaccine Priorities

ALL 6 MONTHS AND OLDER + DON’T WANT THE FLU

HEALTHCARE WORKERS

High risk for disease (symptomatic and asymptomatic)

High risk for transmission

If sick not available to provide healthcare…

PATIENTS @ Highest Risk severe illness/spread

Pregnant women

Newborns and Children < 2 years

Elderly

“Medical Comorbidities” (including Obesity)

Household contacts of high-risk

Long-term care/institutionalized, Crowded living conditionshttp://www.cdc.gov/vaccines/pubs/vis/downloads/vis-flu.pdf

Influenza ‘Nuts and Bolts’1

IIV: 1 dose for adults

Incl: QIV, TIV, sqTIV, hdTIV, LAIV, ccTIV, rHA (Flublock)

Kids < 9 years, first vaccine season: 2 doses 4+ weeks apart

LAIV can be safely used in MOST HC settings as alt. to TIV2

Egg allergy: ACIP, AAAI: NO contraindication.

Anaphalaxis EXCEEDINGLY rare [~1 in 4 million doses]

History is key: Hives= higher risk, consider allergy referral

Risk/benefit of disease vs. vaccine usually favors vaccine… When vaccinating egg-alergic, observe in office ~ 30 minutes

1. http://www.cdc.gov/vaccines/pubs/vis/downloads/vis-flu.pdf 2. http://www.premierinc.com/all/safety/safety-share/12-05-downloads/03-shea-hcw-flu-position-paper.pdf3. http://www.uptodate.com/contents/influenza-vaccination-in-individuals-with-egg-allergy

Influenza Vaccine effectiveness is multifactorial

Match with ‘disease’ strains

Vaccine availability and timing

Patient ‘substrate’: ‘Healthy young < 65’ @ ~60-80% v. ‘Sick older > 65’ @

30-40%

Ongoing vaccine research

Adjuvants

Newer production methods

Higher Ag contenthttp://www.cdc.gov/flu/professionals/antivirals/index.htmhttp://www.cdc.gov/flu/professionals/diagnosis/

Pneumococcal > 2000 Adults 65+ die from invasive Pneumococcal Disease

yearly

Primary adult vaccine is purified capsular polysaccharide [PPS23]

23 types- cause of 88 % bacteremic PNC dz 60-70% efficacy vs. invasive disease [IPD]

IPD= Pneumococcal meningitis, bacteremia Does not ‘prevent pneumonia’

Immunity lasts at least 5 yr. following 1 dose

ROUTINE REVACCINATION ONCE @ 5+ yr. + age 65 ACCEPTED RECOMMEND SELECTED Revaccination:

Vax > 5 yrs before, AND Asplenia, Immunosupressed, CKD or Nephrotic Syndrome

Local reactions- only common AEhttp://www.cdc.gov/vaccines/recs/schedules/downloads/adult/2009/adult-schedule-bw.pdf

PPS 23 Vaccine Effectiveness

7 Meta-Analyses of RCT [Most recent Cochrane 1/2013] Conclusions inconsistent re: cause specific outcomes

Agreement: REDUCTION in IPD; NO reduction ALL CAUSE mortality, pneumonia

3 Meta-Analyses of OBS studies

Consistent results: vaccine is effective for prevention of IPD

Recent RCT Results

IPD: Odds ratio [consistent] 0.26 (CI 0.25-0.46)

Pneumonia: Odds ratio [signif. heterogeneity] 0.71 (CI 0.52-0.97)

Mortality: Odds ratio 0.87 (CI 0.69-1.10)

Summary

Data supports PPS to prevent IPD, not compelling for Pneumonia, Mortality

Fine, et.al. ArchivesIM 1994(154): 2666. Hutchinson et.al. CanJFP 1999(45): 2381. Watson, et.al. Vaccine 2002(20): 2166. Conaty, et.al. Vaccine 2004(22): 3214. Dear, et.al. Cochrane DB Syst Rev 2004, Issue 3. Moberley , et.al. Cochrane DB Syst Rev 2008, Issue 1. Moberly, et.al. Cochrane DB Syst Rev 2013, Issue 1.

Pneumococcal Recommendations

PPS23 is recommended1 for:

Adults 65+

Cigarette Smokers [Since 2009]

Chronic conditions:

Diabetes

Heart, Lung, Liver, Kidney disease Including Asthma [Since 2009]

Immunocompromise [PCV13+PPS Since 2012]

Disease-based: Solid tumor, Hematologic malig, Myeloma, HIV,…

Iatrogenic: Steroids, Organ transplants, BMT, …

Anatomic/functional asplenia [Sickle Cell, etc.][PCV13+PPS Since 2012]

CSF Leak, Cochlear Implant [PCV13+PPS Since 2012]1. MMWR 2008;57(53). 2. Scott, et.al. Vaccine 25 (2007) 6164-6.

Routine PCV-13 in US infants since 2010

2010 FDA approved + ACIP recommended

All children 6 weeks – 71 months [Series- another talk…]

Dec 30, 2011 FDA approves for adults:

Prevention of pneumonia and IPD ≥ 50 years

Based on immunogenicity studies [not clinical efficacy]

Safety in ~6000 adults similar to PPSV23

June 20, 2012 [Pub Oct 12, 2012] ACIP recommends PCV13 in adults:

Immune compromised adults ≥ 19 years + CSF leak/cochlear implant

Best practice PCV 13 should be administered before PPS23

1 Booster in children 6-18 years with immune compromiseACIP. MMWR. 2012:61:394-395.

PCV13 Vaccine in Adults NEW 2012

PCV 13 Recommended in Adults With:

Solid Organ Transplants

Multiple myeloma

Hematologic malignancy [Leukemia, Lymphoma, Hodgkins]

General Malignancy

ESKD, Nephrotic Syndrome

Sickle Cell, hemoglobinopathy

HIV

Immunosuppression/Immunodeficiency

Not-immune-compromised

CSF leak, Cochlear implant

Pneumococcal (PPS23) vaccine-naïve patients:

Adults ≥ 19 yrs with immunocompromise, CSF leak/Cochlear implant

PCV13 FIRST followed by PPS23 at least 8 weeks later

Booster PPS23 in 5 years

AND boost PPS 23 after 5 years PLUS 65+ years old

Previously PPS23-vaccinated subjects:

Adults ≥ 19 yrs with immunocompromise, CSF leak/cochlear implant

PCV13 should be given 1+ years AFTER PPSV23

Booster PPS23 in 5 years

AND boost PPS 23 after 5 years PLUS 65+ years oldACIP. MMWR. 2012:61:394-395; ACIP June 20, 2012.

PCV13 Vaccine in Adults NEW 2012

Td >> Tdap All patients should have primary Tetanus, diphtheria series

3 doses: 0, 1 m., 6 m. [Yields protective Ab ~ all for 10 yrs+]

Many adults > 60 y. never received primary T, d series

Over 50% adults do not have protective T, d Ab’s Booster Td every 10 years [Many adults do not receive routine boosters]

Most boosters given are ‘episodic trauma-related’

Replace 1 dose Td with Tdap [In primary series or as ‘booster’]

Tdap need not wait on 10 year interval from last Td

Td/Tdap Contraindications

Severe allergy to vaccine comp., Arthus reaction after prior Tetanus vax.

[Tdap] Encephalopathy < 7 days after pertussis containing vaccine

[Tdap] Unstable neurologic disease, Moderate-severe acute illness

http://www.cdc.gov/vaccines/vpd-vac/combo-vaccines/DTaP-Td-DT/Tdap.htm

Td >> Tdap Pertussis incidence increasing since 1970’s

2012: CDC Passive Surveillance US >42,000 cases, likely 10+x higher

Community outbreaks: Most in fall, winter and in persons of all ages

Nosocomial Disease: Academic, Community [Med/Surg, OR, L&D, NICU, Oncology]

Residential Care

Adults/Adolescents do not have ‘classic’ triphasic disease

Most have persistent Cough: Median 4 months [6 studies]

20-40 % ‘Whoop’, 40-55 % Posttussive emesis 12-32 % Lymphocytosis

~10% develop complications [Pneumonia most common]http://www.cdc.gov/vaccines/vpd-vac/pertussis/http://www.cdc.gov/vaccines/vpd-vac/combo-vaccines/DTaP-Td-DT/Tdap.htm

Td >> Tdap Tdap Recommendation: All Adults

Single dose to replace one dose Td [Booster or primary] Current recommendation: subsequent Td q10yr

Research on repeated dosing ongoing May give any time (< 10 years) following last Td

2011: Tdap recommendation extended to adults > 65 years

No data to suggest harm Research in process re: effectiveness

Special emphasis: adults with close infant contact:

HEALTHCARE, Parents, Child Care, etc. NEW 2013: Tdap intrapartum all women, each

pregnancy Regardless of interval/prior Tdap [ideal @ 27-35 weeks]http://www.cdc.gov/vaccines/vpd-vac/combo-vaccines/DTaP-Td-DT/Tdap.htm

Zoster Most who have varicella have measureable Ab for life

Zoster occurs when CMI surveillance declines [theoretical]

Reactivation or Varicella exposure re-stimulates CMI [Cycle repeats]

Lifetime risk of Zoster ~33% [99.5% adults serology + prior Varicella]

At 85- lifetime risk ~ 50%

PHN= most common AE To 1/3 patients with Zoster

More common

Zoster occurs @ 70+

Immunocompromised

Vaccination stimulates CMI

Arvin A. NEJM 2005;352:2266-77. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5705a1.htm

Zoster Vaccinate 60+ adults [ACIP: Not immunocompromised]

FDA approved from age 50 [Coverage? Cost/Bene?] Regardless of prior Zoster [opinion: wait 1 yr] No need to test for/vaccinate against Varicella first

Contraindications

Pregnancy Anaphylactic Hypersensitivity to Neomycin, Gelatin No need to defer for ‘at risk contacts’- transmission risk low No need to defer if recent transfusion, Ab containing products

Adverse events

Occasional mild varicella-like rash @ vaccine site

Frozen powdered vaccine: Give within 60 minutes, 0.65 ml SQ Deltoid

Duration of protection: At least 4 years. No booster.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5705a1.htm

ZosterVaccine Efficacy Trial:

38,546 Veterans: Median age: 69 years 60-69: 20,747 [Efficacy greatest in this

group]

≥ 70: 17,799 (46%)

≥ 80: ~2,500 (6.5%)

Excluded: Immunocompromised, prior zoster, < 60 yrs.

Vaccine group had [v. placebo]: 51% fewer episodes of zoster

Less severe disease

66% less postherpetic neuralgia

No significant safety issues were identified Oxman MN et al. NEJM. 2005;352:2271-2284.

Varicella Varicella, Zoster vaccines from OKA-strain attenuated virus

Varicella 1,350 PFU virus/dose

Zoster 20,000-60,000 PFU virus/dose

Varicella recommendations similar to MMR: 2 doses, live virus

Difference: Non-immune born after 1980

Risk of vaccination in pregnancy lower than MMR; but neither is recommended: Vaccinate non-immune women postpartum

Risk groups

HEALTHCARE WORKERS (need 2 doses unless immune) Education, Daycare, Institutional Employees Women of childbearing age [Vaccinate pre-preg., post-

partum] International travel

MMR, Varicella Contraindications:

Severe immune compromise Organ transplant

HIV: CD4 < 200

Allergy to vaccine component [MMR=Egg, Varicella=Neomycin, gelatin]

Acute/severe illness

Recent transfusion [Any immunoglobulin-containing product]

Active untreated TB

Pregnancy MMR: not pregnant x 3 months after vaccine- prevent NRS

Varicella: Not major risk but avoiding all live vaccines recommended

Live virus vaccines [Var., MMR, Zoster] and Tb skin test

OK same day, otherwise delay skin test > 3 monthshttp://www.cdc.gov/mmwr/preview/mmwrhtml/00053391.htm

MMR

Disease reports increased since 2005….

Live-attenuated vaccine, routine childhood in most ‘developed world’

MMR for Adults: 2 doses in non-immune adults born after 1957

High Risk HEALTHCARE WORKERS [Born after 1957- Immune or 2 doses]

College Students, [Prison, military barracks, etc.]

International Travelers Outbreaks assoc. with international travel, adoptions

ImmigrantsCDC Health Advisory Network: June 22, 2011, 16 :00 EST (04:00 PM EST) CDCHAN-00323-11-06-22-ADV-Nhttp://www.cdc.gov/mmwr/preview/mmwrhtml/mm5733a1.htm http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5542a3.htmhttp://www.cdc.gov/mmwr/preview/mmwrhtml/mm5753a6.htm

Hepatitis A, B Vaccination currently recommended in all US children

Hepatitis A [2007]

Hepatitis B [1995]

Both have selective recommendations for adults

Do NOT need to start over if completion of series is delayed

Can be given individually or together [Combination vaccine] HAV: 2 doses @ 6+ month interval

HBV: 3 doses @ 0, 1 m, 6 m. Dose and alternate regimens are different for Hemodialysis patients

Combination: 3 doses @ 0, 1 m, 6 m.

Accelerated Combo.: 4 doses @ 0, 7 d., 21-30 d., booster @ 1 yr.

http://www.cdc.gov/vaccines/recs/schedules/downloads/adult/2009/adult-schedule-bw.pdf

Adult Hepatitis A,B Indications Hepatitis A

Chronic Liver Disease Including chronic HBV, HCV

MSM Injection Drug Users Travel to endemic area Recipients of Clotting

factors Lab workers

Dialysis HBV

High dose vaccine: all ESRD pt.

Hepatitis B Diabetes mellitus [12/2011] Chronic Liver Disease incl. chronic

HCV MSM Injection Drug Users Travel to endemic area/intl. adoption Recipients of Clotting factors >1 sexual partner/6 mo, STD clinics HEALTHCARE WORKERS HIV Household and sexual contacts of HBV

patients Male prison inmates, correctional staff Developmental disability facility

patients, staff AK natives and pacific island natives Any others that want to prevent HBVhttp://www.cdc.gov/vaccines/recs/schedules/downloads/adult/2009/adult-schedule-bw.pdf

HPV Cervical Cancer is consequence of a STD [HPV]

Second most common cause CA death in women 500,000 cases and 250,000 deaths per year

US: ~10 women die every day of cervical cancer

Cause of anal CA and penile CA in men

20 million current HPV infections

By age 50, 80% SA women will have acquired genital HPV Many clear spontaneously

6.2 million new genital HPV infections/year in US 74% in women 15-24 years of age

70% Cervical CA worldwide d/t serotypes 16 [54%], 18 [13%]

>90% Genital Warts due to serotypes 6, 11 http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm

HPV Vaccines:

Gardasil [MSD]: Types 6,11,16,18 3 dose series @ 0, 2 m., 6 m. Cervarix [GSK]: Types 16,18 3 dose series @ 0, 1-2 m, 6 m. Ideally should finish series with same vaccine begun, but mix is OK… Effective protection at least 5 years based on published data [ongoing] Effective only for types patient has NOT previously acquired

HPV 2 or 4 Women 11-12 [9-26]: prevent Cervical CA [Pre-CA], Genital Warts

HPV4 Men 9-26 to prevent anal/penile preCA and CA Contraindications/Cautions:

Local reaction, bronchospasm reported Not recommended in pregnancy- no proven AE [administer after delivery] Immunosupression can reduce efficacy

VACCINE DOES NOT CHANGE CERVICAL CANCER SCREENING RECs!

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm

Meningococcal Highly-contagious gram-negative bacterial infection

Highest mortality in children < 1 year

Recommended for children @ 11-12, pre-college ‘catch up’ selective adult recommendation based on risk

4 Current vaccines: A, C, Y, W-135 [no type B vaccine]

MPS4: Polysaccharide vaccine [SQ, 1 dose +?booster] Available since 1978, fair efficacy, OK if conjugate not available

MCV4 [3 products]: Conjugate vaccines [IM, 1 dose] Approved 2005, 2010, 2012

Preferred for primary vaccination

Selective booster dosing after 5 yrs [e.g. if high risk persists/recurs] MMWR 2005;54(RR-7)

Meningococcal Indications

All Children 11-12 years

College freshmen who will live in dormitory/commune

Not previously vaccinated or vaccinated >5 years previously

Asplenia [anatomic or functional]: Best to vaccinate pre-splenectomy

Terminal complement deficiencies

HIV: Best response if CD4 > 200

Travelers to ‘at risk areas’: Sub-Saharan Africa, Dec-June

Required for entry into Saudi Arabia/Mecca during Hajj

Microbiologists with potential occupational Meningococcus exposure

MMWR 2005;54(RR-7)

Healthcare Workers

Healthcare Workers Key in implementation of Adult Immunization

Education Multiple studies: MD recommendation increases patient Vax

uptake

Need preventive benefits ‘for themselves’

Potential source for disease transmission Patients

Other staff

Communities

Families

Potential for VPD to impair patient care Adversely affect efficiency

Prevent HCW from working with [their] patientshttp://www.cdc.gov/mmwr/preview/mmwrhtml/00050577.htm

HCW Vaccination Annual influenza vaccination

Tdap: All should receive 1 dose

MMR, Varicella: Proof of immunity or 2 doses [each vaccine]

HBV: 3 dose series

Titer 1 month after series; repeat series x 1 if titer < 10 IU

No recommendation for screening titer otherwise

HCW RecommendationsVaccine HCW

RecommendationOther Consideration

Influenza Annual HCW vax. decr. risk to Pt +

Pneumococcal [PPS, PCV]

No HCW Specific Rec. All smokers, 65+, med.ind.

MMR* 2 doses Unless immune, born before ‘57

Varicella* 2 doses Unless immune

HPV No HCW Specific Rec. Rec. all women 9-26 yr.

Td/Tdap Tdap 1 dose, Td Q10yr. Tdap esp. infant contact

HAV Only sel. lab workers All kids [2007 forward]

HBV 3 dose series HBsAb @ 1 mo; If -, rpt series

Meningococcal [MCV]

Only sel. lab workers All 11+ kids [2006 forward]

Zoster* No HCW Specific Rec. Healthy 60+ adults

Adapted from data located at http://www.cdc.gov/vaccines/recs/schedules/adult-schedule.htm

* Live Virus Vaccines

Special Populations Hospitalized [Medical] Patients

Influenza [in season], Pneumococcal year-round

Consider ‘family ring’ Tdap, Influenza prior to L&D discharge

Immune Compromise: Maximal ‘non-live’ vaccination

Steroids: Prednisone 20 mg/d equivalent

HIV: CD4 < 200

Biologic Immunomodulators

Preop Consult

MeningCV, PCV13 then 8+ week PPS23 Pre-Splenectomy

PCV13 then 8+ week PPS 23 Pre-Cochlear implant

Travel

CDC ‘Yellow Book’, Travel Clinics esp. for ‘specials’

Immunization Improvement

Strategies Reminder-Recall

Telephone, E-mail, Text, Post card,..

Partnering

Local Pharmacy, Health Unit

Team-based Care [Standing Orders]

Front desk—MA--Nurse—MD

Standing orders for vaccination are approved and endorsed by CMS since 2002

Regular P-D-S-A Cycling

Internal and External reporting

Tools ACP Adult Immunization Guide

FREE!! I-phone/I-pad App [Available in App store]

Download complete guide [or sections] from ACP website

CDC Adult Immunization Scheduler

http://www.cdc.gov/vaccines/recs/Scheduler/AdultScheduler.htm

CDC/ACIP Recommendations

http://www.cdc.gov/immunizations

http://www.cdc.gov/vaccines/pubs/ACIP-list.htm

IAC Summary of Adult Immuniztion Recs

http://www.immunize.org/catg.d/p2011.pdf

STFM SHOTS Tools for ‘Smart’ Phones

http://www.immunizationed.org/

Thank you for your attention! Questions???