Hot Topics in

Pediatric Infectious Diseases

Ravi Jhaveri M.D.
Assistant Professor of Pediatrics
Duke Childrens Hospital

Objectives
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 these
issues

A gift that keeps on giving

giving.

The impact of PCV7

7 valent
l t conjugate
j
t P
Pneumococcall vaccine
i
The polysaccharide capsules of the 7
serotypes
t
that
th t cause 85% off disease
di
attached
tt h d
to Diphtheria toxin to improve immunogenicity
compared to old 23 valent polysaccharide
vaccine
Approved for use in preventing pneumococcal
disease in children in Feb 2000
Itt has
as had
ad a major
ajo impact
pact o
on invasive
as e d
disease
sease

The impact of PCV7

Kaplan S et al, Pediatrics March 2004 443-9

PCV7 Indirect Benefits

PCV7-Indirect

PCV7 More benefits

PCV7-More
2 studies came out this past year to
elaborate further on benefits of PCV7
One on pneumonia
p
One on meningitis

PCV7 More benefits

PCV7-More
Jan 2009 MMWR examined Pneumonia
h
hospitalizations
it li ti
ffrom 1997
1997-1999
1999 compared
d
to 2005 and 2006
They examined all children under 2 and also
those 2-4 years

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

PCV7 More benefits

PCV7-More

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

PCV7-More benefits

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

PCV7 More benefits

PCV7-More
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 1997-1999
R
Routine
ti Fl
Flu vaccination
i ti iin 6
6-23
23 month
th olds
ld b
began
in 2004

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

PCV7 More benefits

PCV7-More
Hsu et al described the drop in meningitis
cases since
i
th
the iimplementation
l
t ti off PCV7
Compared cases of Pneumococcal meningitis
f
from
1998-2005
1998 2005
Examined data from 8 states
Looked at adults and children

N Engl J Med 2009;360:244-56

PCV7 More benefits

PCV7-More

N Engl J Med 2009;360:244-56

PCV7 More benefits

PCV7-More

N Engl J Med 2009;360:244-56

PCV7 More benefits

PCV7-More

N Engl J Med 2009;360:244-56

PCV7 More benefits

PCV7-More
The bottom line is:
Less cases of meningitis, particularly in the
children who likely received vaccine
Some increase in non-vaccine serotypes with
an accompanying
i rise
i iin resistance
i t
They did see an increase in serotype 19A,
which
hi h h
has b
been receiving
i i a llott off attention
tt ti
lately.
N Engl J Med 2009;360:244-56

The straight story?

A few words about the emergence of
non-vaccine serotypes like 19A
More factors than vaccine may be at play:
Natural shifts in circulating serotypes
Changes in antibiotic use (azithro in
particular)

Bread and Butter?

Changes 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

Changes in AOM

Changes in AOM

Changes in AOM

Changes in AOM
The authors concluded:
Hi
Hi-dose
dose amox had no effect
Vaccine did not have the dominant effect
Large
g scale vaccine trial showed 8% efficacy
y

We have altered our criteria and threshold for

treatment
Likely under pressure to reduce antibiotic use

Taking
g a rightful
g
p
place in the
pantheon..

Not just Viral

Viral Syndrome
Syndrome
R
Recently
tl di
discovered
dP
Parvoviruses
i
called
ll d
Human Bocavirus
Called
C ll d B
Boca b
because it iis related
l t d tto other
th
parvoviruses from cows (BOvine) and dogs
(
(CAnine)
)

Early studies on BoCavirus showed high

g rates of codetection rate,, but also high
infection and inadequate studies of
asymptomatic patients
Still not clear whether pathogen or passenger?

Not just Viral

Viral Syndrome
Syndrome
A study from Brieu et al examined
p
with LRTI vs.
children hospitalized
asymptomatic controls
Used DFA
DFA, Elisa and RT
RT-PCR
PCR
methods to detect the battery of resp
viruses
i
iincluding
l di B
BoCa
C
Pediatr Infect Dis J 2008;27: 969973
969 973

Not just Viral

Viral Syndrome
Syndrome
Found 33 children
with BoCa monoinfection
No significant
differences in high or
low viral load cases
Could detect virus for
several months after
acquisition
q
Pediatr Infect Dis J 2008;27: 969973

Not just Viral

Viral Syndrome
Syndrome

Pediatr Infect Dis J 2008;27: 969973

Not just Viral

Viral Syndrome
Syndrome
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

Id
did
d not
o d
discuss
scuss that
a it may
ay a
also
so infect
ec the
e
GI tract-symptoms?
The
The jury is still out on this.

Death by a thousand cuts

cuts

A novell vaccine
i approach
h
Coleman et al in a July 2008 Science paper
employed
p y a new strategy
gy for developing
p ga
vaccine for Polio
They took advantage of species-specific codon
bias in this study
WARNING:
WARNING The following slides contain BASIC
SCIENCE!!!
Dont worry: I will go slow and explain
Science: 360 (2008):1784-1787

What is codon bias?

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

Despite this redundancy,

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

Let me give an example:

Science: 360 (2008):1784-1787

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:
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
codons
Science: 360 (2008):1784-1787

Using the codon bias

Science: 360 (2008):1784-1787

Using the codon bias

Science: 360 (2008):1784-1787

Using the codon bias

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

The bottom line: A potentially promising vaccine

strategy
Reversion
R
i iis possible
ibl b
butt nott lik
likely
l given
i
th
the
replacement of the entire genome, not specific
site mutations
Science: 360 (2008):1784-1787

Supporting Evidence

Rx for Osteomyelitis
When I first joined the division,
division we would
have vigorous discussions about the
management of children with Osteomyelitis
Some practitioners were wedded to the
notion of exclusive IV therapy to avoid
relapses/treatment failures
I and others disagreed
g
that this was
necessary
Most of the literature on this subject is old and
d
does
nott address
dd
th
the specific
ifi iissue off IV vs. IV
to oral switch

Rx for Osteomyelitis
IIn the
th Feb09
F b09 iissue off Pediatrics,
P di t i
Z
Zaoutis
ti
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

Rx for Osteomyelitis
Aft
After excluding
l di patients
ti t with
ith h
hospital
it l d
data
t
issues, inadequate follow up, co-morbid
conditions,
diti
prolonged
l
d LOS,
LOS th
they h
had
d 1969
evaluable patients

1021 were in the IV group

948 were in the oral switch
S a
S.
aureus
re s and MRSA were
ere 40%
75-80% received either Cefazolin or Oxacillin/Nafcillin
as their IV antibiotic
Pediatrics 2009;123:636642

Rx for Osteomyelitis

Pediatrics 2009;123:636642

Pediatrics 2009;123:636642

Rx for Osteomyelitis
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:
Becoming afebrile
Normal or close to normal CRP, ESR dropping
Child running down the hall

I need more power Scotty

Hep B vaccine NRs

W
We have
h
llong since
i
kknown th
thatt about
b t 10%
dont respond to the 3 dose series of HepB
vaccine
CW: re-try a 3 dose series and some will
respond; the others we hope CMI will
protect them
Cardell et al from Sweden took a different
approach
Journal of Infectious Diseases 2008; 198:299 304

Hep B vaccine NRs

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
Journal of Infectious Diseases 2008; 198:299 304

Hep B vaccine NRs

Results:
All patients
responded
d d with
ith
appropriate antiHAV levels
All but 2 developed
HepB sAb
One had no Ab and
one was 8.5 IU
Journal of Infectious Diseases 2008; 198:299 304

 What is interesting
is that levels of
HepB sAb were
significantly lower
than vaccine nave
Many had a brisk
response after dose
1 suggesting
i
memory responses
Journal of Infectious Diseases
2008; 198:299 304

Just because we can,

does not mean we should

H Pylori
H.
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. pylori
and have been able to decrease
infection/colonization dramatically
What were/are the consequences of this?

H Pylori
H.
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
1999 2000 to
study children 3-19 years
The Journal of Infectious Diseases 2008; 198:553 60

H Pylori
H.

The Journal of Infectious Diseases 2008; 198:553 60

H Pylori
H.

The Journal of Infectious Diseases 2008; 198:553 60

H Pylori
H.
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 has
likely co-evolved with humans
The Journal of Infectious Diseases 2008; 198:553 60

H Pylori
H.
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
The Journal of Infectious Diseases 2008; 198:553 60

Questions?