1 / 35

Richard Whitley, MD Professor of Pediatrics, Microbiology, Medicine and Neurosurgery

Seasonal and Pandemic Influenza: Children, Immunocompromised Hosts, Pregnant Women and Nursing Home Residents. Richard Whitley, MD Professor of Pediatrics, Microbiology, Medicine and Neurosurgery UAB Center for Biodefense and Emerging Infections University of Alabama at Birmingham

beyla
Download Presentation

Richard Whitley, MD Professor of Pediatrics, Microbiology, Medicine and Neurosurgery

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Seasonal and PandemicInfluenza: Children, Immunocompromised Hosts, Pregnant Women and Nursing Home Residents Richard Whitley, MD Professor of Pediatrics, Microbiology, Medicine and Neurosurgery UAB Center for Biodefense and Emerging Infections University of Alabama at Birmingham Birmingham, AL

  2. Pediatrics

  3. 2002-2003 2000-2001 2001-2002 2003-2004 2004-2005 NVSN Influenza Laboratory-Confirmed Cumulative Hospitalization Rayes for Children 0-4 Years, 2004-05and Previous 4 Seasons 14 12 10 8 Polulation-Based Rate per 10,000 Children 6 4 2 0 40-41 42-43 44-45 46-47 48-49 50-51 52-1 2-3 4-5 6-7 8-9 10-11 12-13 14-15 16-17 2004-05 Influenza Season 2 Week Reporting Period

  4. Hospitalization Rates for Patients by Age and Risk Groups (Interpandemic Years) www.cdc.gov.

  5. Influenza In Children… • Flu symptoms in school-age children and adolescents are similar to those in adults. • Temperature of 101°F or above • Cough • Muscle ache • Headache • Sore throat • Chills • Tiredness • Feeling lousy all over • Children tend to have higher temperatures than adults, ranging from 103°F to 105°F. • Flu in preschool children and infants is hard to pinpoint, since its symptoms are so similar to infections caused by other viruses. • If the symptoms mentioned above are present and the flu is in your area, please contact your doctor immediately.

  6. CNS Effects of Influenza • Encephalitis • Myelitis • Guillain Barré Syndrome • Post Infectious Encephalitis

  7. Influenza Associated Pneumonia • Primary Viral Pneumonia • Bacterial Pneumonia (“superinfection”) • S. pneumonia • H. influenzae • S. aureus • Mixed Viral/Bacterial Pneumonia

  8. Timing of 153 Cases of Fatal Influenza in Children - United States, 2003-2004 Season 2004-05 Influenza Season 2 Week Reporting Period 9 8 7 6 5 No. of Cases 4 3 2 1 0 Oct-4 Nov 1 Nov 29 Dec 27 Jun 24 Jun 24 Mar 20 Apr 17 Date of Onset of Illness Bhat, N. et al. N Engl J Med. 2005;353:2559-2567.

  9. Distribution of Cases and Mortality Rates According to Geographic Location and Age Group among 153 Children with Fatal Influenza - United States, 2003-2004 Season *CI denotes confidence interval. †Ages are those on the date of the onset of the illness or, if that information was unavailable, at the date of death. P for trend <0.001 by a chi-square test of age-specific mortality rates. Bhat, N. et al. N Engl J Med. 2005;353:2559-2567.

  10. Influenza-Associated Mortality Rates According to Age Group - United States, 2003-2004 Season 1.00 0.90 0.80 0.70 0.60 Influenza-Associated Mortality(deaths per 100,000 children) 0.50 0.40 0.30 0.20 0.10 0.00 <6 mo 6-11 mo 1 yr 2 yr 3 yr 4 yr 5-10 yr 11-17 yr Age Group Bhat, N. et al. N Engl J Med. 2005;353:2559-2567.

  11. Underlying Health Status of 149 of 153 Children with Fatal Influenza - United States, 2003-2004 Season Bhat, N. et al. N Engl J Med. 2005;353:2559-2567.

  12. Goals for Pediatric Patients • Educational Programs in the School System • Prevention by vaccination • Early Diagnosis and Treatment

  13. --------HAI assay------- --Neutralization assay-- Seroconversion to H3N2 Strains after One Dose of LAIV or TIV in Seronegative Children * Vaccine strain % Seroconversion (>=4-fold rise) P<0.001 P<0.001 78 P<0.001 68 65 P=0.094 20 13 11 4 4 * * Mendelman et al. PIDJ 2004;23:1053

  14. CAIV-T and TIV in Children 6-59 Months • CP-111: pivotal phase 3, direct comparison study during 2004-5 season • 8,492 children, 249 sites, 16 countries • Culture-confirmed influenza (TIV vs CAIV-T): • Matched strains: 1.4% vs 2.4% (44% reduction) • Mis-matched strains: 6.2% vs 2.6% (58% reduction) • All strains: 8.6% vs 3.9% (55% reduction) • AE and SAE rates comparable • Post-immunization (to day 42) wheezing in primary vaccinees < 2 yr old: 2.0% vs 3.2%

  15. Influenza Treatment in Children: Primary Endpoint Time to resolution of all illness *P<0.001 compared to placebo recipients, using weighed Mantel-Henszel test, stratified for region and otitis media.

  16. Influenza Treatment in Children: Secondary Endpoint Time to return to normal health and activity *P<0.001 compared to placebo recipients, using weighed Mantel-Henszel test, stratified for region and otitis media.

  17. Influenza Treatment in Children: Tertiary Endpoint Number of subjects with Otitis Media(without OM at baseline)

  18. 9 8 7 6 5 Active metabolite RenalClearance (ml/min/kg) 4 3 (approximate adult value) 2 1 0 0 2 4 6 8 10 12 14 16 18 Age (y) Oseltamivir Exposure in Children (2 mg/kg) Y = 0.45x + 9.49 R2 = 0.59 P < 0.001 Oo et al. Paediatr Drugs. 2001;3:229.

  19. Detection Of Antiviral Resistant Influenza During Treatment Roberts N. Phil. Trans R Soc Lond. 2001;356:1895. Kiso et al. Lancet. 2004;364:759.

  20. Pregnant Women

  21. Adjusted Incidence Rates of Acute CardiopulmonaryEvents per 10,000 Women-Months of Observation by Medical Risk and Pregnancy Status, Among Women High Risk Women Neuzil et al. Amer J Epidemiol. 1998;148:1098.

  22. Adjusted Incidence Rates of Acute CardiopulmonaryEvents per 10,000 Women-Months of Observationby Medical Risk and Pregnancy Status, Low Risk Women Neuzil et al. Amer J Epidemiol. 1998;148:1098.

  23. H3N2 H3N2 H3N2 H3N2 H3N2 B H1N1 H3N2 B B H3N2 B B B H3N2 H1N1 H1N1 Excess Acute Cardiopulmonary Events per 10,000 Person-Months During Influenza Season by Year and Risk Group for High-Risk and Low-Risk Women Neuzil et al. JAMA. 1999:281:905.

  24. Immunocompromised Hosts

  25. Influenza in Transplant Recipients: Clinical • Immunocompromised patients suffer more complications and have higher morbidity and mortality from influenza infection • High rate of hospitalization and ICU admissions • Higher rate of pulmonary complications • 50% of BMT and 13% renal transplant patients had lower respiratory tract infections • 50% of BMT and 7% of renal transplant patients with influenza complicated by pneumonia • 63% progressed to pneumonia • 43% mortality

  26. Influenza in Transplant Recipients: Clinical • Higher rate of extrapulmonary complications • 42% incidence of neurologic symptoms • Rejection or graft dysfunction • Hepatic decompensation • High rate of rejection • Increased mortality • 13-40% mortality secondary to influenzain the BMT populations • 23% mortality in a pediatric transplant population

  27. Influenza in Transplant Recipients: Outcomes

  28. Prolonged Viral Shedding Influenza in Transplant Recipients: Virology 1.00 Kaplan-Meier survival estimates, by donor2 0.75 0.50 donor2 2 0.25 donor2 1 0.00 0 10 20 30 40 Analysis Time

  29. Treatment of Influenza in Immunocompromised

  30. Nursing Home Residents

  31. The Association of Resident Influenza Vaccination Status in Nursing Home Size with the Occurrenceof Influenza Outbreaks *P = .023. Arden et al. Amer J Pub Health. 1995;85:399-401.

  32. Conditional Logistic Regression Analyses of Influenza Vaccine Effectiveness in Preventing Influenza-like Illness and Pneumonia Ohmit et al. JAGS. 1999;47:165-171.

  33. Research Needs • Natural History of Influenza in High Risk Populations: • Immunocompromised host and • Pregnant women • Clinical Trials of Antiviral Agents in At-Risk Patients • Monotherapy • Combination Therapy • Will resistance occur more frequently?

  34. Pediatric Initiatives • Current vaccine recommendations are for administration at 6 and 23 months. What about older children • Extend recommendations • Use of cold adapted influenza vaccine • Oseltamivir can not be administered to infants < 1 year of age • Neurotoxicology assessments in animal models • PK and PD studies in infants

More Related