Al-Hertani, W.

Bortolussi, R.

Byers, D.

Yan, S.R.

International Journal of Infectious Diseases

Elsevier - Publisher Connector 

11 Lipopolysaccharide (LPS) induced priming of human newborn polymorphonuclear neutrophils (PMN) is diminished due to decreased levels of MyD88 and attenuated p38 phosphorylation 

$6 International Journal o[ In[ectious Diseases (2006) 10($1 ) Abstracts 
whereas, other risk factors, such as diabetes met- 
titus, neutropenia, corticosteroid therapy, and iron 
toad, previously reported in older patients were 
virtually non-existent. No apparent underlying con- 
dition was found in 4 neonates (12%). The most 
common patterns of zygomycosis were dissem- 
inated (49%), gastrointestinal (24%), deeply ex- 
tended (15%) and cutaneous (6%) disease. 15 (45%) 
cases were diagnosed by histology only and 18 (55%) 
by histology and culture. Among 18 culture- 
confirmed cases, Rhizopus pp. were isolated from 
14 (78%) cases with mortality of 50%. Among 12 pa- 
tients who were given antifunga[ therapy, 7 re- 
ceived an amphotericin B formulation only, white 5 
received an amphotericin B formulation combined 
with other antifunga[ agents. However, 21 patients 
received no antifunga[ therapy. Overall mortal- 
ity was 26/33 (79%) as compared to 56.4% for 
children >30d and 52.8% for adults (CID 41:634, 
2005; p < 0.02). Mortality was not significantly re- 
lated with decade of publication, gender or race. 
Mortality was tower (2/7 or 29%) among patients 
who received an amphotericin B formulation than 
among neonates who received no antifunga[ ther- 
apy (21/21 or 100%, p=0.0002); 16 (48%) neonates 
underwent surgery. With exception of two cuta- 
neous cases that were both cured, at[ other pat- 
terns of zygomycosis carried a mortality rate ~>83%. 
Conclusions: Zygomycosis an extremely serious 
infection in neonates with a high mortality and 
strong propensity to disseminate. Amphotericin B 
formulations ignificantly improve outcome. 
10 
Parvovirus B19 and Nlyocarditis in an Infant 
C. Hassib*, N. Sekarski, R Mey[an, R Roux- 
Lombard, B. Vaudaux. Centre Hospitalier 
Universitaire Vaudois, Lausanne, Suisse 
Background: Parvovirus B19 (PV B19) infection can 
cause a wide spectrum of disease syndromes. It is 
emerging as a new and important candidate for my- 
ocarditis and subsequent dilated cardiomyopathy 
(DCM) in immunocompetent and immunocompro- 
raised children. 
The mechanism of PV B19 induced post natal my- 
ocarditis and subsequent DCM is different from that 
in other viral myocarditides and is characterized by 
infection of intracardiac endothelial celts of small 
arterioles and veinu[es, with endothelial dysfunc- 
tion, impairment of myocardial microcircu[ation, 
penetretion of inflammatory celts and eventually 
myocyte necrosis. Recent data suggest that the 
cytokines interferon-gamma, tumor necrosis factor 
alpha and inter[eukin-6 and -8, wich are observed 
at high levels in PV B19-associated myocarditis in 
children in addition to microcircu[atory dysfunc- 
tion, contribute to myocardial damage and inflam- 
mation. 
We report a case of life-threatening PV B19 DCM 
secondary to PV B19 myocarditis in immunocom- 
petent toddler. The aim of this paper is to alert 
clinicians to the rote of PV B19 in infant myocarditis 
and DCM. 
11 
Lipopolysaccharide (LPS)Induced Priming 
of Human Newborn Polymorphonuclear 
Neutrophils (PMN) is Diminished due to 
Decreased Levels of MyD88 and Attenuated 
p38 Phosphorylation 
W. A[-Hertani, S.R. Yan, D. Byers, R. Borto[ussi* 
Dalhousie University, Halifax, Nova Scotia, Canada 
Background: Diminished response of po[ymor- 
phonuc[ear neutrophi[s (PMN) to [ipopo[ysaccharide 
(LPS) has been implicated in the increased sus- 
ceptibility of human newborns to Gram-negative 
bacteria[ infections. LPS activates or primes PMN 
for a variety of host defense functions including 
enhanced production of oxidative radicals (respi- 
ratory burst), a process that is known to involve 
the Mitogen-Activated Protein (MAP) kinase p38. 
Objectives: To determine the celt signaling path- 
ways that may contribute to the attenuation of 
priming for newborn PMN. 
Methods: PMN were isolated from newborn um- 
bilical cord and adult blood. PMN [ysates were 
separated on SDS PAGE and probed for MAP ki- 
nases, Toil-like Receptor-4 (TLR-4), Mye[oid Differ- 
entiation Factor 88 (MyD88) using Western blotting. 
Functional activation was assayed after stimulation 
with LPS using flow cytometry to determine CD66b 
upregu[ation as an indicator of degranu[ation. 
Results: We found that p38 phosphory[ation i
newborn PMN is attenuated in response to LPS 
stimulation even though adult and newborn PMN 
have similar amounts of p38 protein. The degree 
of attenuation in newborn PMN was dependent on 
the osmo[arity of the medium. In addition, LPS- 
induced degranu[ation, a process that is p38 de- 
pendent, was also absent in newborn PMN. We also 
assessed LPS receptors on PMN and observed that 
white TLR-4 is present at similar levels on newborn 
and adult PMN, its downstream adaptor protein 
MyD88 was significantly diminished in newborn PMN 
compared to adult celts. 
Conclusion: Although the mechanism of PMN prim- 
ing by LPS is not fully understood, our results 
suggest hat MyD88 and p38 phosphory[ation are 
Infections in Neonates, Pediatrics and the ELderLy $7 
important pathways in the process and contribute 
to attenuated response of newborn PMN to LPS in 
vitro. 
12 
Infection and Distribution Patterns of Beta and 
Gamma Herpesviruses in Waldeyer's Ring Tissue 
C. Berger*, M. Hug, D. Nadat. Division o[In[ectious 
Diseases, University Children's Hospital of Zurich, 
8032 ZUrich, Switzerland 
Background: The Lymphoid tissue of the orophar- 
ynx acts as a portal of entry and exit and as reser- 
voir for the human beta and gamma herpesviruses 
(HHV) foLLowing primary infection and estabLish- 
ment of Latency. 
Objective: To elucidate frequencies and quantities 
of the human beta HHV (HHV-5, -6, -7) and gamma 
HHV (HHV-4, -8) in adenoids and palatine tonsils. 
Methods: We determined the presence and the 
quantities of HHV-4, -5, -6, -7 and -8 in autoLogous 
adenoids and palatine tonsils from children under- 
going three-tonsiLLectomy for medical reasons using 
in-house established quantitative poLymerase chain 
reaction assays with Lower detection Limits ranging 
between 2 and 10 HHV DNA copies/~g DNA. 
Results: HHV-4 (Epstein-Barr virus) was detected 
in 80% of the organs from 30 children, HHV-5 (cy- 
tomegaLovirus) in 637o, and HHV-6 and HHV-7 in 77% 
each. HHV-8 was not detected. If detectable in a 
patient, HHV-4 was found in 73% in both adenoid 
and tonsils, HHV-5 in 237O, HHV-6 in 407O, and HHV-7 
in 53%. The number of DNA copies of a given HHV in 
autoLogous adenoids and tonsils significantly corre- 
Lated for HHV-4 and HHV-7 (p = 0.04 and p = 0.0007, 
respectively), but not for HHV-5 and HHV-6. The 
HHV DNA LeveLs correlated between HHV-5 and 
HHV-6 in adenoids and tonsils (p = 0.01 and p = 0.02, 
respectively) and between HHV-5 and HHV-7 in 
tonsils (p = 0.04), but not between other HHV. 
Conclusions: The different correlations of quanti- 
tative contents in autoLogous adenoids and tonsils 
suggest for HHV-5 and HHV-6 infection and distri- 
bution patterns distinct from those of HHV-4 and 
HHV-7. 
13 
Randomized Controlled Trial of Oral vs. 
Sequential Intravenous/Oral Cephalosporins 
in Dimercaptosuccinic Acid (DMSA) 
Scintigraphy-documented Acute Pyelonephritis 
in Children 
C. Berger, K. Buechner, E. Girardin*, U. WiLLi, 
T.J. Neuhaus, D. NadaL For the Swiss 
Pyelonephritis Study Group. Divisions of 
Infectious Diseases, University Children's Hospital 
of Zurich, Zurich, Switzerland 
Background: No study has assessed the efficacy and 
safety of oral antibiotics in children with DMSA- 
documented pyeLonephritis. 
Objectives: To compare efficacy and safety of oral 
versus sequential intravenous/oraL cephatosporin 
treatment of acute pyeLonephritis in children. 
Methods: 235 children aged 6 months to 16 years 
with a febrile urinary tract infection - rectal tem- 
perature >38 °, C-reactive protein (CRP) >10mg/t, 
and bacterial growth in cultures from urine coL- 
Lected by catheter - were prospectively randomly 
assigned to receive either intravenous ceftriaxone 
(50 mg/kg once daily) for 3 days, foLLowed by oral 
ceftibuten (9 mg/kg once daily) for 11 days or oral 
ceftibuten for 14 days. A first DMSA scintigraphy to 
detect acute renal Lesions was performed within 
5 days. Micturition cystogram and 2nd DMSA were 
performed after 6 weeks and 6 months, respec- 
tively. ExcLusion criteria were complex renal maL- 
formations and septicat appearance. 
Results: 150 children (64?o; 132 females (f) and 
18 males (m); median age 25 months, range 6-189) 
had acute renal Lesions on DMSA. 71 (47%; 61 f, 
10 m; median age 20 months) were given cetri- 
axone/ceftibuten, 79 (53%; 71 f, 8 m; median 
age 27 months) ceftibuten. One patient from the 
oral regimen only had to be switched to intra- 
venous therapy due to repeated vomiting. The 
2nd DMSA showed persistent Lesions (scars) in 
33 children (46?o; 29 f, 4 m) treated with ceftriax- 
one/ceftibuten versus 19 (24%; 18 f, 1 m) treated 
with ceftibuten (p = 0.004). 
Conclusions: In children with DMSA-documented 
pyeLonephritis, oral antibiotic therapy for 14 days 
with once daily ceftibuten is effective, safe 
and convenient, and resulted in significantly 
tess renal scars than sequential intravenous/oraL 
cephatosporin therapy. 


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11 Lipopolysaccharide (LPS) induced priming of human newborn polymorphonuclear neutrophils (PMN) is diminished due to decreased levels of MyD88 and attenuated p38 phosphorylation

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