Hot Topics in Pediatric ID

Robert J. Leggiadro, MDChairmanDepartment of PediatricsLincoln Medical Center

Professor of Clinical PediatricsWeill Medical College of Cornell University

NY Times Headline 10/14/08

• Worrisome Infection Eludes a leading Children’s Vaccine

Emergence of Pneumococcal Serotype 19A

• Most common invasive serotype

• Largest proportion resistant IPD

JID 2008; 197:1016-27.

From The Journal of Infectious Diseases 197(7):1016–1027.© 2008 by the Infectious Diseases Society of America.For permission to reuse, contact journalpermissions@press.uchicago.edu.

Figure 1. Age-specific incidence of invasive pneumococcal disease caused by serotype 19A, 1998–2005

Native Alaska Children less than 2 yrs.

• PCV7 coverage 90%

• Since 2004 140% ↑ in NV strains

• 30% 19A; others 3, 6A, 7F

• Vaccine covered strains ↓ 96%.

Copyright restrictions may apply.

Singleton, R. J. et al. JAMA 2007;297:1784-1792.

Cases of Invasive Pneumococcal Disease by Serotype Among Alaskan Children Younger Than 2 Years, 1995-2000 and 2001-2006

Copyright ©2008 American Academy of Pediatrics

Ongkasuwan, J. et al. Pediatrics 2008;122:34-39

FIGURE 1 Histogram of the annual number of cases of pneumococcal mastoiditis, and the proportion that were serotype 19A, among children at Texas Children's Hospital

between 1995 and June 2007

Copyright ©2008 American Academy of Pediatrics

Ongkasuwan, J. et al. Pediatrics 2008;122:34-39

FIGURE 4 Histogram of the annual number of total pneumococcal isolates, and the proportion that were serotype 19A, recovered from middle ear fluid cultures obtained

from children at Texas Children's Hospital between 1995 and June 2007

Emergence of Pneumococcal Serotype 19A

• Equally capable of IPD, NP colonization and AOM.

• 9th most common IPD serotype pre-PCV7; common NP carriage pre-PCV 7

• High rate of resistance

• PCV7 ineffective against 19A

Emergence of Pneumococcal Serotype 19A

• Clonal expansion

• Capsular switching

• Selective advantages

Emergence of PneumococcalSerotype 19A

• PCV7 may not be the only factor

• Antibiotic (especially macrolide) use impacts serotype distribution

• Alaska, Barcelona, Israel, China, Belgium

• White Mountain Apache population has not seen 19A increase

Pneumococcal Meningitis Epidemiology in the PCV7 Era

• 2001 – 2004 compared with 1994 – 1999• 2/3 reduction in rates of PM in children less than

2 yrs old• 1/3 reduction in rates of PM in adults 65 yrs and

older• Median age ↑ to 46 yrs from 37 yrs.• Overall 3,300 cases, 394 deaths of PM

prevented.

Clin Infect Dis 2008; 46:1664

Epidemic Pneumococcal Meningitis in Africa

• Ghana, Burkina Faso

• Concurrent with meningococcal epidemics

• Dry season

• Serotype 1 most common

Epidemic Pneumococcal Meningitis in Africa

• Underappreciated burden of pneumococcal disease in sub-Saharan Africa.

• Unique propensity of serotype 1 S. pneumoniae to cause serious infection and out breaks.

• Opportunity for prevention through pneumococcal vaccination.

Bacteremia among children in Rural Kenya

• Hospital deaths in children between 60 d and 5 y• 8.7% due to pneumococcal bacteremia• 4.9% due to H. flu bacteremia• Highlights need for prevention through

immunization

N Engl J Med 2005; 352:39-47.

Childhood Bacteremia in Rural Kenya

•28% children hospitalized with bacteremia died

•26% hospital deaths associated with bacteremia

•Bacteremia responsible for more deaths than malaria (22%)

PCV Worldwide

• Only 26 (14%) of 193 WHO members have introduced PCV7 into their national immunization programs.

• Primarily high-income countries with relatively few childhood deaths secondary to IPD.

IPD Mortality Indicators in Children less than 5 years old

•More than 50 deaths/1,000 live births•50,000 deaths annually•More than 10% deaths secondary to Pn

•Greater than 1% HIV incidence in adults

Pneumococcal Conjugate Vaccines

• PCV7; 14, 6B, 19F, 9V, 23F, 18C, 4

• PCV10; 7 plus 1, 5, 7F

• PCV 13; 10 plus 3, 6A 19A

Role of Bacterial Pneumonia1918 – 1919 Influenza Pandemic

•Bacterial pneumonia on autopsy•Typical pneumonia features•Picture similar to measles 1917-1918•Most influenza typical, including full recovery•Mortality reflected bacterial pneumonia rates•Higher rates in U.S. military camps•Time of onset (10 d) consistent with bacteria pneumonia•Early bed rest effective in isolation from bacterial carriers

JID 2008; 198:962-70

Bacterial Pneumonia and Pandemic Influenza Planning

• Shift in focus• Basic research• Pneumocococcal vaccines• Source, supply, surge capacity of important

antibiotics• Inclusion of vancomycin• Implications for developing countries

Emerg Infect Dis 2008; 14:1187-92