Infectious Disease Consult

Educational Objectives

The goal of this program is to improve prevention of infectious diseases in children through adherence to recom­mended vaccination schedules and discouragement of practices that cause antibiotic resistance. After hearing and as­similating this program, the clinician will be better able to:

1.   Recognize risks associated with the growing incidence of Chagas disease in the United States.

2.   Immunize pediatric patients within recent guidelines for vaccination.

3.   Consider treatment with an oral antiviral agent in infants testing positive for cytomegalovirus.

4.   Appropriately counsel parents who refuse or are reluctant to have their children vaccinated.

5.   Implement practices that prevent increases in resistance to antibiotic therapy and discourage the spread of re­sistant strains of bacteria.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or com­mercial interest. For this program, the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Steele spoke at 6th Annual Update in Pediatrics, held July 30-31, 2010, in New Orleans, LA, and sponsored by Ochsner for Children. Dr. Ryan spoke at Hiltonhead: Island Partners: 5th Annual Dermatology and Pediatric Topics for Primary Care Practitioners, presented July 12-16, 2010, at Hilton Head Island, SC, and sponsored by Geisinger Health System. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.

Recent Infectious Disease Publications That Have or Should Have Changed Your Practice

Russell W. Steele, MD, Division Head, Pediatric Infectious Diseases, Ochsner Children’s Health Center, New Orleans, LA

Chagas disease: associated with reduviid bug (nicknamed “kissing bug” due to predilection for lips); prevalent in Central and South America, but increasingly observed in North America; recent study from Arizona found »50% of Triatoma reduviidae carry Trypanosoma cruzi (cause of Chagas disease)

Cases: most recent case in United States occurred in 2006 in New Orleans; case published in 2007; case identified shortly after initiation of routine screening; 193 positive tests reported by blood banks over 9 mo (translates to nationwide prevalence of »300,000); only 11% of positive donors contacted Centers for Disease Control and Pro­tection (CDC); study conclusion highlighted lack of physician awareness

Impact: affects nearly 8 million people in Mexico, Central America, and South America; one-quarter (2 million) have cardiomyopathy; Chagas disease most frequent cause of need for heart transplantation in that region

Treatment: recommended for acute and congenital infections, immunosuppressed patients, and children £18 yr of age; treatment of adults based on, eg, epidemiologic factors, travel history (eg, 50-yr-old with history of recent first-time travel to South America may have acute disease); disease associated with severe anaphylaxis in some cases; cases reported in Louisiana, California, and Arizona

Vaccine update: development of safe effective vaccines considered major achievement of past decade; new vaccines  —  meningococcal conjugate (Menveo); human papillomavirus (HPV; Cervarix); measles, mumps, ru­bella, and varicella zoster (ProQuad); pneumococcal 13-valent conjugate (Prevnar-13); H1N1 flu

HPV vaccine: Cervarix covers 2 strains of HPV; reduces incidence of cervical cancer by £70%; may offer antibody protection against other cancer-causing strains (evidence-based data not yet available); antibody titer levels re­main higher over several years; considered equivalent to Guardasil, but does not prevent genital warts

Meningococcal conjugate vaccines: Menveo approved for patients 11 to 55 yr of age, but may be approved for all patients as young as 2 yr of age (alternative vaccine [Menactra] approved for high-risk patients ³2 yr of age); ap­plication for novel conjugate vaccine (MenHibrix; covers Haemophilus influenzae type b and prevalent sero­groups C and Y) recently filed; immunization given at 2, 4, and 6 mo of age; need for 12-mo booster being evaluated; serogroup C immunization in young children resulted in herd immunization in England and Canada

HPV vaccine in men: now approved for prevention of genital warts (with decrease in cervical cancer in partners an­ticipated); reimbursement for vaccine provided by Aetna, Blue Cross, Blue Shield, and Cigna, and Medicaid (but not all insurance companies)

Pneumococcal conjugate vaccine (PCV): PCV13 covers 6 additional types of Pneumococcus, including type 19A (virulent pathogen more likely to cause meningitis, bacteremia, and severe infection); approved for children 6 yr of age in accordance with recent guidelines; covered by Vaccines for Children (VFC) despite slight increase in cost (compared to 7-valent conjugate vaccine); one dose recommended in children £5 yr of age with previous 7-valent conjugate vaccination; approved for use in high-risk patients £18 yr (eg, with sickle cell disease, HIV, im­munosuppression), in addition to 23-valent vaccine; speaker would recommend for children without high risk and adults, but reimbursement not available

Rotavirus vaccine: standard rotavirus vaccine (Rotarix) found to be contaminated by pig virus in March 2010; alter­native vaccine (RotaTeq) not contaminated; Rotarix vaccine temporarily suspended, but now considered safe by Food and Drug Administration (FDA); RotaTeq later found to contain same virus in minute quantities; both vac­cines currently approved and included in VFC program

Rabies vaccine: current recommendation includes 4 total vaccine doses (vs previous recommendation of 5 doses); recommendation based on data indicating vaccine success with 3 to 4 doses; subsequent evaluation of antibody titers in patients receiving <5 but >2 doses validated current recommendation

Booster dose of meningococcal vaccine: need in preadolescents confirmed in study providing serogroup C vaccine in young children and adolescents; children immunized at 2 mo of age found to have decreased antibody titers by 6 yr of age; therefore concluded that children immunized in first year of life require booster at 6 to 12 yr of age

Other pediatric issues

Congenital cytomegalovirus (CMV): 1% of babies have congenital CMV; standard treatment includes 6 wk intrave­nous (IV) antiviral therapy (ganciclovir) if central nervous system involvement suspected; recent data from Japan indicate that oral valganciclovir (16 mg/kg twice daily) as effective against CMV as IV ganciclovir (allows treat­ment without lengthy hospitalization; also encourages treatment of children with more subtle findings, which may help in preventing cases of hearing loss due to CMV); routine treatment with oral valganciclovir of children positive for CMV on blood spot test under consideration

Severe combined immunodeficiency (SCID): American Academy of Pediatrics (AAP) recommended uniform screening for SCID in January 2010; performed via blood spot test utilizing polymerase chain reaction (PCR) that detects T-cell receptor; low SCID prevalence (1 in 50,000 to 100,000) balanced by high rate of success (95%) of transplantation when performed in children with SCID at <2 mo of age; Wisconsin screening of 71,000 infants had 8 positive results (including one child with lymphopenic syndrome who received life-saving bone marrow transplantation)

Influenza: H1N1 influenza more severe in children than in adults; study in college dormitory found significant re­duction in influenza incidence (£50%) in students using face masks and hand hygiene (measures considered ef­fective in shared-living situations); Canadian study of Hutterite communities indicated that immunization of children confers herd immunity to adult population

Mastitis: incidence £33%; associated with Staphylococcus aureus, Group A Streptococcus, and Corynebacterium; chronic mastitis often caused by Staphylococcus epidermidis; in recent study, investigators generated oral Lacto­bacillus from L fermentum and L salivarius recovered from breast milk; treatment of women with Lactobacillus therapy associated with lower bacterial counts and lower rates of recurrence of infection, compared to those given traditional antibiotics

Hot Topics in Pediatric Infectious Disease

Michael E. Ryan, DO, Associate Chief Medical Officer and Chairman of Pediatrics, Janet Weis Children’s Hospital, Geisinger Health System, Danville, PA

Vaccination Controversies

Background: parental concerns about safety primary reason for refusal of childhood vaccinations; fear caused by propaganda in media and limited parental knowledge of diseases (believe that diseases have been eradicated); non­vaccination also caused by fear of adverse reaction despite dramatic decrease in incidence over past several decades

Autism: research published by Wakefield linked measles vaccine to autism based on biopsy specimens; flaws of study include undisclosed conflict of interest, erroneous manipulation of data, and deception and misreported re­sults (all other authors subsequently withdrew from publication); reinterpretation of data failed to reveal associa­tion; author’s medical license revoked in United Kingdom

Thimerosal: linked in independent research to mercury toxicity in premature infants; no additional evidence found, but compound subsequently removed from immunizations with no change in outcomes, according to Institute of Medicine and FDA; thousands of lawsuits about thimerosal persist today; rate of autism continues to increase de­spite removal of thimerosal from vaccines (studies suggest genetic basis for autism)

Refusal of vaccination: most religions support immunization (including Amish); AAP encourages universal vacci­nation, but fails to stringently apply medical neglect laws to parents who choose not to vaccinate their children; fail­ure to routinely vaccinate affects quality of care provided by pediatricians and complicates accurate diagnosis of symptomatic children; most pediatric practices intolerant of parents who refuse vaccination; vaccine efficacy evi­denced by outbreaks of disease among nonvaccinated children worldwide (eg, current pertussis outbreak in Los Angeles); global travel exacerbates ease of transmission of disease

Human papillomavirus: 2 effective HPV vaccines available (bivalent and quadrivalent); recommended for girls 11 to 12 yr of age; administered in 3 doses over 6 mo in children ³9 yr of age; catch-up vaccination recommended for women £26 yr of age; »30 to 35 million doses now being administered; vaccine nearly 100% effective, with 92% of adverse effects (AEs) nonserious (eg, pain at injection site, fainting); have patients sit in office for 15 min af­ter vaccination to prevent harm if fainting occurs; serious AEs rare and generally considered unrelated to vaccine (including death); vaccine now mandatory in several states; issues influencing routine administration  —  cost of mandatory vaccination; continued safety concerns; perceived encouragement of promiscuous behavior (discussion of vaccine ideal for initiating conversation on sexual activity; emphasize preventive nature of vaccine [ie, best to vaccinate before sexual activity begins]); vaccine costly to both practice and patient and not always covered by in­surance; expired or wasted vaccines negatively affect cost margins; many private practices now coordinate efforts to prevent expiration of supplies; VCF program covers cost of vaccine

Influenza: H1N1 strain incorporated into standard influenza vaccine this year; highest rate of influenza vaccination observed last year (including both standard and H1N1 doses); H1N1 epidemic occurred between September and November 2009, but no seasonal flu epidemic observed last year (attributed either to coverage by H1N1 vaccina­tion, or high rate of standard flu vaccination); no serious AEs associated with H1N1 vaccine; influenza vaccine comes in inactivated (injection) or live attenuated (droplet) forms; live attenuated form considered more effica­cious, confers greater immunity against mismatched strains, and may provide more immediate protection during outbreaks; mist contraindicated in individuals >50 yr of age and asthmatic patients (although evidence of exacerba­tion of asthma scarce); pregnant women should receive inactivated vaccine (may confer passive protection to baby)

Pneumococcal conjugate vaccine: patients with full PCV7 immunization still require PCV13 booster dose due to addition of 6 additional strains; adminstration of pneumococcal vaccine polyvalent (Pneumovax 23) recommended 8 wk after PCV13 dosing (possibly to cover strain 6A)

Antibiotic Resistance

Common resistant pathogens: Group A streptococci (becoming resistant to macrolides); pneumococci (showing re­sistance to b-lactams); enterococci (strains resistant to vancomycin seen); resistant strains of Clostridium difficile and Mycobacterium tuberculosis seen worldwide

Mechanisms of resistance: drug inactivation or modification (eg, b-lactam production); altered drug target sites (eg, altered penicillin-binding protein); altered metabolic pathway; reduced drug accumulation (via efflux pumps and decreased permeability); preventing drug resistance  —  avoid parental arguments over antibiotics with education about lack of efficacy for viral infections and reasonable timeframes for resolution; provide treatment of symp­toms (eg, analgesics)

Methicillin-resistant S aureus (MRSA): cephalexin (Keflex) considered ineffective; methicillin resistance defined as minimal inhibitory concentration (MIC) ³4 μg/mL; resistance continues to increase (estimated 1%-2% of pop­ulation or 3 to 6 million people now colonized); many infected patients have no risk factors for MRSA; cases of hospital-acquired MRSA decreasing, while cases of community-acquired MRSA increasing; infections increas­ing in seriousness and frequency, with majority being skin and soft tissue infections; treat with incision and drainage (I and D) plus clindamycin, tetracycline, or trimethoprim-sulfamethoxazole (Bactrim); discourage lanc­ing at home; submit culture for confirmation of pathogen type; invasive disease becoming more common; tips to prevent MRSA  —  practice good hygiene (especially of hands); perform I and D; utilize bleach baths (one-half cup bleach in 13 gal water, soak for 15 min twice weekly; ideal for skin infections)

Suggested Reading

Bortolussi R, Salvadori M: A new meningococcal conjugate vaccine: what should physicians know and do? Paediatr Child Health. 2009 Oct;14(8):515-20; David MZ, Daum RS: Community-associated methicillin-resistant Staphylococ­cus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev. 2010 Jul;23(3):616-87; Dinleyici EC: current status of pneumococcal vaccines: lessons to be learned and new insights. Expert Rev Vaccines. 2010 Sept;9(9):1017-22; Fombonne E: Thimerosal disappears by autism remains. Arch Gen Psychiatry. 2008 Jan;65(1):15-6; Hale JE et al: Identification of an infant with severe combined immunodeficiency by newborn screen­ing. J Allergy Clin Immunol. 2010 Oct 6 [Epub ahead of print]; Johnson N et al: The immune response to rabies virus infection and vaccination. Vaccine. 2010 May;28(23):3896-901; Lescure FX et al: Chagas disease: changes in knowl­edge and management. Lancet Infect Dis. 2010 Aug;10(8):556-70; Markowitz LE et al: Quadrivalent human papilloma­virus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007 Mar;56(RR-2):1-24; Rodrigo C et al: Recommendations for rotavirus vaccination: a worldwide perspective. Vac­cine. 2010 Jul;28(31):5100-8; Salmon DA, Siegel AW: Religious and philosophical exemptions from vaccination re­quirements and lessons learned from conscientious objectors from conscription. Public Health Rep. 2001 Jul-Aug;116(4):289-95; Seasonal trivalent influenza vaccine for 2010-2011. Med Lett Drugs Ther. 2010 Oct;52(1348):77-9; Syggelou A et al: Congenital cytomegalovirus infection. Ann NY Acad Sci. 2010 Sept;1205:144-7; Wakefield AJ: MMR vaccination and autism. Lancet. 1999 Sept;354(9182):949-50.