INFECTIOUS DISEASE UPDATE
| NEW AND FUTURE VACCINES —Stephen C. Eppes, MD, Clinical Associate Professor, Department of Pediatrics, Jefferson
Medical College of Thomas Jefferson University, Philadelphia, PA; Infectious Disease Specialist, Division of Infectious
Diseases, Alfred I. DuPont Hospital for Children, Wilmington, DE
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| Pertussis: epidemiology—ranked worst among vaccine-preventable diseases; during last 20 yr, number of reported cases
increased dramatically; in 2006, worst epidemic of pertussis seen during last 50 yr in United States, mostly in adolescents
and young adults; underreported; true incidence (based on seroepidemiologic studies) probably 1 to 3 million/yr,
with ≈1 million cases in children ≥15 yr of age; factors influencing increasing incidence—improvement in diagnosis,
surveillance, and reporting; polymerase chain reaction (PCR) testing; waning vaccine-induced immunity (patients have
10-15 yr of protection after natural infection and 6 yr of protection after vaccine); morbidity and mortality—severe
disease usually seen in infants; hospitalizations and complications, eg, pneumonia, seizures, encephalopathy, occur
more frequently in infants <6 mo of age (less frequent but still problematic in infants 6-11 mo age); deaths in 1980s predominantly
in unimmunized infants 0 to 1 mo of age; in 1990s, distribution by age same as in 1980s, but deaths due to
pertussis among unimmunized infants 0 to 1 mo of age doubled; transmission—Centers for Disease Control and Prevention
(CDC) study found source of pertussis infection usually family member, eg, mother; to stop transmission, need
to target immunization efforts in adolescents and adults, not just infants; clinical manifestations in adolescents and
adults—prolonged cough (3 wk) most common manifestation; also paroxysm, whoop, and posttussive emesis; associated
with absenteeism at school and work; meta-analysis found cases of prolonged cough associated with pertussis etiology
in 12% to 50% of patients
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 | Vaccine: DTaP (diphtheria and tetanus toxoids and acellular pertussis vaccine, adsorbed) first generation of acellular pertussis
vaccine; DTaP available in combination vaccines; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis,
adsorbed (Tdap; adolescent and adult booster); Bordetella pertussis—produces pertussis toxin (PT);
attachment proteins include filamentous hemagglutinin (FHA), pertactin (PRN), and fimbrial agglutinogens (FIM);
adolescent Tdap booster—Boostrix and Adacel; use reduced amount of acellular pertussis components; safe and immunogenic;
Food and Drug Administration (FDA)-approved and available; antigenic components of DTaP and
Tdap—Infanrix, vaccine for infants, contains PT, FHA, PRN, and DT toxoids; Boostrix contains reduced amounts of
same antigens in Infanrix; Daptacel, vaccine for infants, contains PT, FHA, PRN, FIM (2 and 3), and DT toxoids;
Adacel contains reduced amounts of same antigens in Daptacel; FDA approval requires 1 dose of Tdap in adults to be
as immunogenic as 3 doses of DTaP in infants; Canadian study appears to show effectiveness in reducing pertussis infection
rate; only Adacel approved for use in adult population; Advisory Committee on Immunization Practices
(ACIP) recommendations for adolescents—routine immunization with Tdap at 11 to 12 yr of age; catch-up immunization
for patients 13 to 18 yr of age who missed earlier immunization; encourage adolescents 11 to 18 yr of age who
have had tetanus and diphteria toxoids (Td) to receive Tdap to protect against pertussis; administer meningococcal
conjugate vaccine 4 (MCV-4) with Tdap at separate sites if both vaccines available and indicated (sequential administration
acceptable); routine use of Tdap during pertussis outbreak; administer Tdap in age-appropriate patient with
wound prone to tetanus; use in persons with history of pertussis infection; use Tdap, followed by 2 doses of Td in persons
never immunized; consider use of Tdap during second or third trimester of pregnancy; American Academy of
Pediatrics (AAP) recommendations for adolescents—similar to ACIP; recommends giving pregnant adolescents
Tdap during second or third trimester of pregnancy; Tdap after Td vaccination—ACIP prefers Tdap administration
after ≥5 yr following Td; study looking at children vaccinated with Td between 18 mo and 9 yr before Tdap administration
found no differences in safety and immunogenicity among individuals; concluded 2-yr minimum interval safe;
ACIP provisional recommendations for Tdap use in adults—1-time, routine Tdap administration for adults to replace
Td booster; Tdap also replaces Td administration during wound management; consider use of shorter interval (2
yr) for pertussis protection in patients with risk factors; adults with close contact to infants biggest risk factor (eg, parents,
grandparents, daycare workers, health care workers [HCW]); pertussis and HCW—5% of adult population; rate
of pertussis infection almost twice that of general adult population; often index case in pediatric and adult outbreaks
occur in health care facilities; Tdap and pregnancy—immunize women anticipating pregnancy and immediately
postpartum; Tdap and elderly patients—Tdap not licensed for use in adults >65 yr of age; currently, Tdap not recommended
for this population; cost-benefit—cost-effective vaccine
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| Rotavirus: associated with ≈0.5 million deaths annually worldwide, mostly in underdeveloped countries
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| Immunization
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| RotaShield: effective vaccine but associated with toxicity; produces fever and gastrointestinal (GI) side effects; linked
with increased incidence of intussusception; withdrawn from market within 1 yr of introduction
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| RotaTeq: FDA-approved and available; pentavalent bovine-human reassortant rotavirus (live) vaccine; studied in
>70,000 infants in 12 countries; 3-dose vaccine; safe and effective; studies show 98% reduction in severe disease,
96% reduction in hospitalization, and 93% decrease in ED visits after 3 doses of vaccine during first season; during
second season, rates of protection slightly reduced; compared to placebo, RotaTeq had 2% to 3% risk for adverse
events and no risk for intussusception; bovine rotavirus less pathogenic than rhesus rotavirus in humans; associated
with fewer GI side effects; ACIP recommendations include routine universal immunization of infants in United
States at 2, 4, and 6 mo of age, with first dose at 6 and 12 wk, and all doses completed by 32 wk; breast-feeding does
not interfere with vaccine; AAP recommendations pending
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| Rotarix: live attenuated monovalent human rotavirus vaccine; not yet FDA-approved
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| Human papillomavirus (HPV): most common sexually transmitted infection worldwide; 75% of all new infections occur
between 15 to 24 yr of age; 75% of women infected during lifetime with ≥1 HPV serotypes, but most patients clear
within 36 mo; causes genital warts and most preinvasive and invasive cancers of lower anogenital tract; HPV 16 and 18
cause most cervical cancers; substantial economic burden associated with HPV; associated with cancers, including cervical,
anal, penile, scrotal, vulvar, vaginal, and some head and neck; recurrent respiratory papillomatosis in children also associated
with HPV infection
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| Vaccines: Gardasil—FDA-approved for young women 9 to 26 yr of age; contains virus-like particles (VLP) from serotypes
6, 11, 16, and 18; multiple clinical trials concluded vaccine well tolerated; involves series of 3 shots (effective in
preventing cytologic changes and against clinical disease); ACIP recommends 3-shot series given to girls 11 to 12 yr of
age (can start as early as 9 yr of age); also recommended for women 13 to 26 yr of age, preferably prior to onset of sexual
activity; AAP recommendations pending; Cervarix—VLP vaccine against HPV 16 and 18; not yet approved by FDA;
several clinical trials found it well tolerated; 3-shot series; concerns—perception that vaccine prevents sexually transmitted
diseases (STD) or that vaccine encourages riskier sexual behaviors; inform patient that vaccine prevents cancer,
not STD; Papanicolaou test still recommended
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| Varicella zoster virus (VZV): in 2005, ACIP recommended vaccinating students entering middle school, high school,
and college; assess women for immunity prenatally, and, if not immune, vaccinate at completion of pregnancy before
discharge from health care facility; vaccinate individuals >13 yr of age without evidence of immunity with 2 doses of
vaccine 4 to 8 wk apart; vaccinate individuals who received only 1 dose with second dose during outbreak; criteria for
immunity included in recommendations (now need documentation of immunity)
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| VZV vaccine: combined live and attenuated measles, mumps, rubella, and varicella (MMRV) vaccine—eg, ProQuad;
large cohort study found similar safety and efficacy, compared to MMR vaccine alone or varicella vaccine
alone, except for slightly higher rate of fever and measles-like rash in MMRV recipients; initial ACIP recommendations
called for single routine dose at 1 yr of age and 2 catch-up doses for 13 yr of age; ACIP now recommends all children
receive second dose of varicella vaccine; varicella zoster immune globulin (VZIG)—no longer available;
passive immunization recommended in people at high risk (eg, immunocompromised children, women, premature infants);
VariZIG—not yet FDA-approved (can get on compassionate use basis)
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| Zoster vaccine: eg, Zostavax; studies in adults show effective in reducing incidence of zoster, burden of illness, and postherpetic
neuralgia; most effective in adults ≥60 yr of age; duration of effectiveness 4 yr; adverse events generally mild; contraindicated
in immunocompromised patients (live-virus vaccine); theoretic risk for transmission of attenuated virus
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| INFECTIOUS DISEASE CONSIDERATIONS DURING AND AFTER NATURAL DISASTERS —Duc J. Vugia, MD,
MPH, Chief, Infectious Diseases Branch, California Department of Health Services, Berkeley
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| Outbreaks of communicable disease after disasters: CDC investigations—Blake reviewed 27 natural disasters
occurring 1970 to 1985, resulting in 3 outbreaks of communicable diseases (ie, balantidiasis after typhoon, mild respiratory
disease after flood, and typhoid fever after cyclone); Toole extended review of natural disasters to 1992, documenting total of
38 disasters that resulted in 6 outbreaks of communicable diseases (included diarrheal disease after flood in Sudan); data show
outbreaks of infectious diseases after natural disasters not common
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| Public health considerations: natural disasters—floods, hurricanes, typhoons, tsunamis, earthquakes, volcanic
eruptions; tornados, fires, heat waves, and cold waves not of concern in general (occur rapidly; do not result in large numbers
of displaced individuals); famine—individuals during famine nutritionally and immunologically deficient and more
susceptible to disease; factors to consider—infectious diseases during or after natural disaster generally caused by
pathogens in affected area; lack of public health and medical care after disaster increases risk for infection; potential for
compromised food and water safety; crowding of displaced persons may increase risk for disease transmission; disease
vectors (eg, mosquitos, rodents, flies) may increase in numbers after disasters
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| Floods, hurricanes, and tsunamis: concerns—during acute phase, most morbidity and mortality due to trauma and
drowning, not infectious diseases; in recovery phase, see wound infections, tetanus, and aspiration pneumonia; waterborne diseases
dependent on pathogens present in area where disaster occurred; consider food- and waterborne diseases, respiratory infections,
and GI illnesses among displaced persons in crowded conditions with poor hygiene; vectors increase, but in United
States, control often initiated immediately following disaster, and outbreaks rare; infectious diseases of concern following
floods—malaria, cholera, diarrheal disease, typhoid fever, hepatitis A, measles, leptospirosis; no outbreaks, except Vibrio illness
in 22 people, occurred after hurricane Katrina; no outbreaks, except small number of cases of unusual rare infections, occurred
after tsunami in Indian Ocean in 2004; vector-borne diseases—review of vector-borne diseases following hurricanes
and floods in United States 1975 to 1997; of 12 disasters, detected arboviral disease activity in 9; only Red River flood in North
Dakota and Minnesota in 1975 resulted in increased transmission of western equine encephalitis and St. Louis encephalitis to
humans and animals; address mosquito-transmitted diseases after floods have occurred
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| Geophysical disasters: considerations—no infectious disease concerns during earthquake; morbidity and mortality
due to trauma during acute phase following earthquake; during recovery phase, potential for wound infections and tetanus;
crowded conditions and poor hygiene may lead to food- and waterborne diseases, respiratory infections, and GI illness
(more likely in developing countries); 1994 Northridge earthquake—coccidioidomycosis outbreak occurred; 203
cases, including 3 fatalities; disease onset peaked 2 wk after event; persons ≥40 yr of age at increased risk; large dust
clouds, generated by landslides and aftershocks in mountains, associated with acute infection; recent review—identified
516 earthquakes, 89 volcanic eruptions, and 16 tsunamis; found only 3 reported communicable disease outbreaks (measles
after volcanic eruption, malaria after earthquake, and coccidioidomycosis after earthquake)
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| Recommendations to prevent outbreaks after natural disaster: consider nature of disaster; displacement of individuals
that results in crowded conditions and poor hygiene of concern (high risk for spread of infectious disease); after
flood or storm, look at pathogens indigenous to area where disaster occurred; to decrease risk for disease—may need
vector control; provide safe water and food and adequate methods of hygiene for displaced persons; reestablish medical
care to treat wounds and prevent sporadic infections; reestablish public health functions, primarily surveillance to detect
cases, impose isolation or quarantine of contagious persons, and possibly mass vaccination to prevent diseases and outbreaks;
vaccinations—give tetanus toxoid if not current; provide hepatitis B series for first responders if exposure to
blood and body fluids anticipated; hepatitis A vaccine recommended for evacuees of hurricane Katrina living in crowded
shelters, but not for responders exposed to contaminated flood water (hepatitis A vaccine not currently recommended routinely
for flood exposure in United States); consider measles vaccine in shelters in developing countries and cholera and
typhoid vaccines, depending on local shelter situations
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Educational Objectives
| The goal of this program is to educate the listener about new and future vaccines and infectious disease considerations during
and after natural disasters. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Discuss the changing strategies in pertussis immunization.
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| 2. Assess the rotavirus, human papillomavirus, and varicella zoster virus vaccines for effectiveness.
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| 3. Describe the potential adverse events associated with each vaccine.
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| 4. List infectious disease outbreaks following natural disasters from 1970 to 1992 reviewed by the Centers for Disease
Control and Prevention.
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| 5. Discuss how to prevent an infectious disease outbreak after a natural disaster.
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Discussed on This Program
Cholera vaccine
Diphtheria and tetanus toxoids, combined (DT; Td)
Diphtheria and tetanus toxoids, adsorbed
Diptheria and tetanus toxoids and acellular pertussis vaccine, adsorbed (DTaP) [Daptacel, Infanrix, Tripedia]
Hepatitis A vaccine, inactivated [Havrix, Vaqta]
Human papillomavirus vaccine [Gardasil]
Measles, mumps, and rubella virus vaccine, live [M-M-R II]
Measles, mumps, rubella, and varicella vaccine, live (MMRV) [ProQuad]
Rotavirus vaccine [RotaShield] (withdrawn)
Rotavirus vaccine live [RotaTeq]
Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap) [Adacel, Boostrix]
Typhoid vaccine [Typhim Vi, Vivotif Berna]
Varicella virus vaccine [Varivax]
Varicella-zoster immune globulin (human) (VZIG) (discontinued)
Varicella-zoster immune globulin [VariZIG] (investigational)
Whole-cell pertussis vaccine (wP)
Zoster vaccine live [Zostavax]
Suggested Reading
Cunliffe NA et al: A critical time for rotavirus vaccines: a review. Expert Rev Vaccines. 4:521, 2005; Davis MM et
al: Physician attitudes and preferences about combined Tdap vaccines for adolescents. Am J Prev Med. 31:176, 2006;
Freed GL et al: Use of a new combined vaccine in pediatric practices. Pediatrics. 118:e251, 2006; Gregory DS: Pertussis:
a disease affecting all ages. Am Fam Physician. 74:420, 2006; Kahn JA et al: Human papillomavirus vaccines
and adolescents. Curr Opin Obstet Gynecol. 17:476, 2005; Lieberman JM et al: The safety and immunogenicity of a
quadrivalent measles, mumps, rubella and varicella vaccine in healthy children: a study of manufacturing consistency and
persistence of antibody. Pediatr Infect Dis J. 25:615, 2006; Ligon BL: Infectious diseases that pose specific challenges
after natural disasters: a review. Semin Pediatr Infect Dis. 17:36, 2006; Linhares AC et al: Vaccines against rotavirus
and human papillomavirus (HPV). J Pediatr (Rio J). 82:S25, 2006; Tai JH et al: Rotavirus vaccination and intussusception:
can we decrease temporally associated background cases of intussusception by restricting the vaccination schedule?
Pediatrics. 118:e258, 2006.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue, Dr. Eppes is
on the Speakers’ Bureaus of Sanofi Pasteur and Merck.
Dr. Eppes was recorded August 4-6, 2006, in Hyannis, MA, at the Cape Cod Conference on Pediatrics, sponsored by
Nemours Children’s Clinic. Dr. Vugia was recorded June 1-3, 2006, in San Francisco, CA, at Advances and Controversies
in Clinical Pediatrics, sponsored by the University of California, San Francisco, School of Medicine. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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