studies use genetic tests to distinguish bacterial infections from viral
infections in children and infants with fever.
children, RNA expression signatures helped distinguish bacterial
infections from other causes of infections
febrile infants age 60 days or younger, RNA bio-signatures could help
distinguish serious bacterial infections
genetic means of identification and advances in this field would reduce
the morbidity, mortality and costs associated with caring for febrile
studies have been conducted which examine the use of genetic tests to identify
if the cause of fever in children
is due to
bacterial or viral infections and also to help rule out serious bacterial
infections in infants with fever. The studies appear in the online journal
1 - To distinguish
bacterial infections from viral infections and other causes in children with
‘RNA sequencing may prove to be an effective alternative to identify bacterial infections in febrile children and infants which would help clinicians to avoid invasive procedures, antibiotics, and hospitalizations when they are not
cases of fever in children are self-remitting viral infections while some can
be life-threatening bacterial infections. Due to only minor differences in
clinical features, sometimes serious bacterial infections are missed out while
children with minor viral infections are prescribed antibiotics
study conducted by Micheal Levin, F.R.C.P.C.H of Imperial College, London and
his colleagues determine whether bacterial infections in children with fever
can be distinguished from other causes by the pattern in which the host genes
are activated or suppressed in response to an infection during the inflammatory
process and if a subset of these genes could be identified for further
in the United Kingdom, United States, The Netherlands and Spain participated
and children with fever presenting to these hospitals were studied from
were places in discovery or validation groups and after microbiological
investigations, each group was classified as having definite bacterial
infection, definite viral infection or indeterminate infection.
diagnostic performance was assessed in the validation group, RNA expression
signatures using blood samples helped distinguish viral from bacterial
infections in the discovery group.
with meningococcal diseases (n=24) and inflammatory diseases (n=48) required
discovery group had 240 children with
median age of 19 months.
It included 52 children with
definite bacterial infection, and among them 36
(69%) required intensive care, and 92 with
definite viral infection, of whom 32 (35%) required
intensive care. Ninety-six children had infection of indeterminate
Blood RNA transcriptomic signatures that distinguished bacterial from
viral infection with 2 gene transcripts, were identified by researchers
The RNA signature also helped
infection from childhood inflammatory diseases, systemic
lupus erythematosus, juvenile idiopathic arthritis, and discriminated
bacterial from viral infection in published adult studies
six percent of the children in the indeterminate group were
classified as having bacterial infection, and among them 95% received antibiotic treatment.
Using transcriptomic signatures for diagnosis
requires the translation of multi-transcript signatures into
clinical tests suitable for hospital laboratories or at the bedside.
state that, "The disease risk score signature, distinguishing
viral from bacterial infections with only 2 transcripts, has potential to be
translated into a clinically applicable test using current technology such as
polymerase chain reaction.
Furthermore, new methods for rapid detection of nucleic acids, have potential for low-cost, rapid
analysis of multitranscript signatures."
"This study provides preliminary data regarding
test accuracy of a 2-transcript host RNA signature discriminating bacterial
from viral infection in febrile children. Further studies are needed in diverse
groups of patients to assess accuracy and clinical utility of this test in
different clinical settings."
2 - To identify
bacterial infections in febrile infants aged 60 days or younger
infants presenting with fever are at a substantial risk of bacterial infection
and the current culture based diagnosis has limitations.
new study by Octavio Ramilo, M.D., of
Nationwide Children's Hospital, Columbus, Ohio, and colleagues examined whether RNA bio-signatures would help distinguish
febrile infants with and without serious bacterial infections.
for this vulnerable population has been affected by lack of optimal management
strategy and has led to unnecessary exposure of many infants to
potential harm. The analysis of host response to inflammation
triggered by infection has been considered as an alternative. Microarray analysis of blood leukocytes (white cells)
helps to identify the pathogen induced host response of RNA bio-signatures.
study involved febrile infants who were 60 days
or younger and were evaluated for fever
in 22 emergency departments from December 2008 to December 2010 .
underwent laboratory evaluations including blood cultures. A
random sample of infants was selected for RNA bio-signature analysis. The healthy infants without fever served
as controls. Blood samples were collected for cultures and RNA bio-signatures.
RNA bio-signatures were defined using bioinformatics tools and febrile infants were classified by
were 1,883 febrile infants with
a median age of 37 days. RNA biosignatures were measured in 19 afebrile
healthy infants and randomly selected 279 infants (89 with bacterial infections--including 32 with bacteremia and 15
with urinary tract infections--and 190 without bacterial infections). Sixty-six
classifier genes were identified which helped to
distinguish febrile infants with and
without bacterial infections in the test set. Ten classifier genes helped
in distinguishing infants with
bacteremia from those without bacterial infections in the test set.
preliminary study helped distinguish febrile infants 60 days or younger with or
without bacterial infections. To validate the accuracy of the test and clinical
use of RNA biosignatures, further research on larger population is necessary
results of these 2 preliminary studies represent promissory notes. "Clearly,
RNA sequencing and other techniques for RNA quantitation are in the early days
of development and evaluation for clinical applications,"
Howard Bauchner, M.D., Editor in Chief, JAMA, Chicago, in an
substantial decline in the prevalence of serious bacterial infection, following
the introduction of conjugate vaccines, has made clinical decision making more
difficult--the needle has become much smaller, and the haystack much larger,
particularly in young infants."
if the promises of findings reported in the studies by Mahajan and colleagues
and Herberg and colleagues are fulfilled by replication and refinement in other
rigorous investigations, it may be possible that such advances will further
reduce morbidity, mortality, and costs associated with caring for febrile
"The day when a parent of a febrile child may do a laboratory test at
home, call a physician, and mutually decide if that child should be seen for
evaluation may soon be here." he adds.
- Studies explore use of genetics to help determine appropriate treatment for fever in children - (http://www.eurekalert.org/pub_releases/2016-08/tjnj-seu081816.php)