hot_topics_jhaveri.pdf

Hot Topics in Pediatric Infectious Diseases

Ravi Jhaveri M.D.Assistant Professor of Pediatrics

Duke Childrens Hospital

ObjectivesObjectives

Introduce or reacquaint you with issues that have been of interest in clinical practice or medical literature

Review the relevant literature that addresses the key points regarding theseaddresses the key points regarding these issues

A gift that keeps on givingA gift that keeps on giving.

The impact of PCV7The impact of PCV7

7 l t j t P l i 7 valent conjugate Pneumococcal vaccine The polysaccharide capsules of the 7

t th t 85% f di tt h dserotypes that cause 85% of disease attached to Diphtheria toxin to improve immunogenicity compared to old 23 valent polysaccharidecompared to old 23 valent polysaccharide vaccine

Approved for use in preventing pneumococcalApproved for use in preventing pneumococcal disease in children in Feb 2000

It has had a major impact on invasive diseaset as ad a ajo pact o as e d sease

The impact of PCV7The impact of PCV7

Kaplan S et al, Pediatrics March 2004 443-9

PCV7 Indirect BenefitsPCV7-Indirect Benefits

PCV7 More benefitsPCV7-More benefits

2 studies came out this past year to elaborate further on benefits of PCV7

One on pneumoniap One on meningitis


Jan 2009 MMWR examined Pneumonia h it li ti f 1997 1999 dhospitalizations from 1997-1999 compared to 2005 and 2006 They examined all children under 2 and also

those 2-4 years

MMWR, January 16, 2009, 58(1):1-4


MMWR, January 16, 2009, 58(1):1-4

PCV7-More benefitsPCV7-More benefits

MMWR, January 16, 2009, 58(1):1-4


A few caveats to this study: It is impossible to directly say PCV7 is

responsible for this effect We do other things in this group that we did

not do routinely in 1997-1999R ti Fl i ti i 6 23 th ld b Routine Flu vaccination in 6-23 month olds began in 2004

MMWR, January 16, 2009, 58(1):1-4


Hsu et al described the drop in meningitis i th i l t ti f PCV7cases since the implementation of PCV7

Compared cases of Pneumococcal meningitis f 1998 2005from 1998-2005

Examined data from 8 states Looked at adults and children

N Engl J Med 2009;360:244-56


N Engl J Med 2009;360:244-56


The bottom line is: Less cases of meningitis, particularly in the

children who likely received vaccine Some increase in non-vaccine serotypes with

i i i i tan accompanying rise in resistance They did see an increase in serotype 19A,

hi h h b i i l t f tt tiwhich has been receiving a lot of attention lately.

N Engl J Med 2009;360:244-56

The straight story?The straight story?

A few words about the emergence of non-vaccine serotypes like 19A

More factors than vaccine may be at play:More factors than vaccine may be at play: Natural shifts in circulating serotypes Changes in antibiotic use (azithro inChanges in antibiotic use (azithro in

particular)

Bread and Butter?

Changes in AOMChanges in AOM

AOM is among the top reasons for child medical visits and #1 reason for Abx use

Sox et al from Boston (his middle name is not Red or Bo) looked at the rate of treatment failure for AOM in the community over a 9 year period Did a separate assessment of hi-dose Amox


The authors concluded: Hi-dose amox had no effectHi dose amox had no effect Vaccine did not have the dominant effect

Large scale vaccine trial showed 8% efficacyg y

We have altered our criteria and threshold for treatment

Likely under pressure to reduce antibiotic use

Taking a rightful place in the g g ppantheon..

Not just Viral SyndromeNot just Viral Syndrome

R tl di d P i ll d Recently discovered Parvoviruses called Human Bocavirus

C ll d B b it i l t d t th Called Boca because it is related to other parvoviruses from cows (BOvine) and dogs (CAnine)( )

Early studies on BoCavirus showed high detection rate, but also high rates of co-, ginfection and inadequate studies of asymptomatic patients

Still not clear whether pathogen or passenger?


A study from Brieu et al examined children hospitalized with LRTI vs. pasymptomatic controls

Used DFA Elisa and RT PCR Used DFA, Elisa and RT-PCR methods to detect the battery of resp i i l di B Cviruses including BoCa

Pediatr Infect Dis J 2008;27: 969973Pediatr Infect Dis J 2008;27: 969 973


Found 33 children with BoCa mono-infectioninfection

No significant differences in high ordifferences in high or low viral load cases

Could detect virus forCould detect virus for several months after acquisitionq

Pediatr Infect Dis J 2008;27: 969973


Pediatr Infect Dis J 2008;27: 969973


What does this study tell us: BoCavirus is a real pathogen but likely

weaker than Flu/RSV based on this data Need a susceptible host

I did not discuss that it may also infect the d d o d scuss a ay a so ec eGI tract-symptoms?

The jury is still out on this.The jury is still out on this.

Death by a thousand cutsDeath by a thousand cuts

A l i hA novel vaccine approach

Coleman et al in a July 2008 Science paper employed a new strategy for developing a p y gy p gvaccine for Polio

They took advantage of species-specific codon bias in this study

WARNINGWARNING: The following slides contain BASIC SCIENCE!!!

Dont worry: I will go slow and explainScience: 360 (2008):1784-1787

What is codon bias?What is codon bias?

If you recall back to your med school studies of protein translation, there is redundancy of the protein codeprotein code GCC,GCT,GCA,GCG: all encode Alanine

Despite this redundancy we know that some of Despite this redundancy, we know that some of these codons are overrepresented (the bias) GCC is 4x more common than GCGGCC is 4x more common than GCG

Let me give an example:

Science: 360 (2008):1784-1787

What is codon bias?What is codon bias?

The code is its preferred form: Death and Taxes The code in a less preferred form: Death and Taxes One more example: One more example:

Please come again (preferred) Yall come back now, ya hear! (?preferred in some

places)

The investigators took a Polio protein and replaced the genetic code with the less represented codonscodons

Science: 360 (2008):1784-1787

Using the codon biasUsing the codon bias

Science: 360 (2008):1784-1787

Using the codon biasUsing the codon bias

Th i ti t t k th i i l t d ith The investigators took the mice inoculated with the attenuated virus and challenged with WT PolioPolio All the mice were protected

The bottom line: A potentially promising vaccine strategy

R i i ibl b t t lik l i th Reversion is possible but not likely given the replacement of the entire genome, not specific site mutations

Science: 360 (2008):1784-1787

Supporting EvidenceSupporting Evidence

Rx for OsteomyelitisRx for Osteomyelitis

When I first joined the division we would When I first joined the division, we would have vigorous discussions about the management of children with Osteomyelitismanagement of children with Osteomyelitis

Some practitioners were wedded to the notion of exclusive IV therapy to avoidnotion of exclusive IV therapy to avoid relapses/treatment failures

I and others disagreed that this was gnecessary

Most of the literature on this subject is old and d t dd th ifi i f IV IVdoes not address the specific issue of IV vs. IV to oral switch


I th F b09 i f P di t i Z ti In the Feb09 issue of Pediatrics, Zaoutis and colleagues performed such a study They looked at kids 2 mos-17 yrs with

Osteo from 2000-2005 at 29 childrens hospitals across the country

They examined those patients that received IV for full course vs. those that switched to oral antibiotics

They looked at treatment failure and associated IV complications Pediatrics 2009;123:636642


Aft l di ti t ith h it l d t After excluding patients with hospital data issues, inadequate follow up, co-morbid

diti l d LOS th h d 1969conditions, prolonged LOS, they had 1969 evaluable patients 1021 were in the IV group 948 were in the oral switch

S a re s and MRSA ere 40% S. aureus and MRSA were 40% 75-80% received either Cefazolin or Oxacillin/Nafcillin

as their IV antibiotic

Pediatrics 2009;123:636642


Pediatrics 2009;123:636642


Bottom line: Oral switch is just as efficacious for osteomyelitis and avoids the complications of prolonged IV therapy

There are certain indicators we use to make the switch:make the switch:

Becoming afebrile Normal or close to normal CRP, ESR droppingNormal or close to normal CRP, ESR dropping Child running down the hall

I need more power Scotty

Hep B vaccine NRsHep B vaccine NRs

W h l i k th t b t 10% We have long since known that about 10% dont respond to the 3 dose series of HepB vaccinevaccine

CW: re-try a 3 dose series and some will respond; the others we hope CMI willrespond; the others we hope CMI will protect them

Cardell et al from Sweden took a different Cardell et al from Sweden took a different approach

Journal of Infectious Diseases 2008; 198:299 304


They decided to use the HepA-HepB vaccine in 3 doses at 0,1 and 6 months They had 48 NRs and 20 vaccine nave

subjects These were all adults aged 20-69 They measured those that reached >10 IUs of

Ab and also measure what the absolute level of HepB sAb to see if there were differences



Results: All patients

d d ithresponded with appropriate anti-HAV levelsHAV levels

All but 2 developed HepB sAbHepB sAb One had no Ab and

one was 8.5 IU


What is interesting is that levels of HepB sAb wereHepB sAb were significantly lower than vaccine navethan vaccine nave Many had a brisk

response after dose 1 i1 suggesting memory responses


Just because we can, does not mean we shoulddoes not mean we should

H PyloriH. Pylori

Marshall and Warren won the Nobel Prize in Medicine in 2005 for their work linking H. pylori with PUD and gastric cancer

From before and since that time, we have treated many many people for H. pyloriand have been able to decrease infection/colonization dramatically

What were/are the consequences of this?What were/are the consequences of this?

H PyloriH. Pylori

Chen and Blaser published a paper in the Aug 2008 that investigated the link between H. pylori eradication and asthma prevalence in children

They used the NHANES 1999-2000 toThey used the NHANES 1999 2000 to study children 3-19 years

The Journal of Infectious Diseases 2008; 198:553 60

H PyloriH. Pylori


H PyloriH. Pylori

The inverse correlation held up when controls for socioeconomic status and HSV-1 and Toxoplasma status were included

The authors discuss that H. pylori is highly interactive within its environment and hasinteractive within its environment and has likely co-evolved with humans


H PyloriH. Pylori

Given that it has persisted this long, it may some other purpose besides just a pathologic one

This same group has performed research showing that while gastric cancer rates have gone down, esophageal cancer rates are going up and certainly we know about the rising rates of atopic diseases


Questions?

hot_topics_jhaveri.pdf

Documents

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benefitsn engl j med

benefits of pcv7

childrenn engl j med

t ti f pcv7cases

valent polysaccharide

nonvaccine serotypes