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INFLUENZA A (H1N1) - WORLDWIDE (69): OTHER VIRAL INFECTIONS
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A ProMED-mail post
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International Society for Infectious Diseases
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Date: Thu 18 Jun 2009
Source: Eurosurveillance, Volume 14, Issue 24, 18 Jun 2009 [edited]
<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19242>
A variety of respiratory viruses found in
symptomatic travellers returning from countries
with ongoing spread of the new influenza A(H1N1)v
virus strain
By: P Follin1, A Lindqvist1, K Nystrom1, M Lindh2
At: 1. Department of Communicable Disease
Prevention and Control, Region Vastra Gotaland,
Sweden, 2. Department of Virology, Sahlgrenska
University Hospital, Gothenburg, Sweden
Clinical specimens from 79 symptomatic
individuals with a recent history of travel to
countries with verified transmission of influenza
A(H1N1) virus (North America) were tested with a
multiple real-time PCR targeting a broad range of
agents that may cause acute respiratory
infection. This analysis revealed that besides 4
cases of influenza A(H1N1) virus, other
respiratory viruses were diagnosed in almost 60
percent of the samples. These observations are a
reminder that many different viral transmissions
occur simultaneously in countries with ongoing
spread of influenza A(H1N1) virus. The findings
demonstrate that the definition of suspected
cases by clinical and epidemiological criteria
has only a poor capacity for discriminating
influenza A(H1N1)v from other viral infections.
Background
A new influenza A(H1N1) virus variant has spread
globally since its 1st appearance in April 2009
[1,2] and as of 17 Jun 2009, there were 39 620
cases reported by the World Health Organization
(WHO) [3]. On 30 Apr 2009, the European
Commission suggested a case definition [4], which
has been adopted and modified by most authorities
in the European Union Member States. In agreement
with this recommendation, testing for influenza A
was recommended in Sweden for cases with a
clinical presentation including respiratory
symptoms and fever above 38 C and epidemiological
circumstances such as recent travel (within 7
days) to areas where the new influenza has been
observed [5] or close contact with confirmed
cases.
The regular sentinel surveillance for seasonal
influenza has been extended and now focuses on
identification of imported cases with influenza
A(H1N1) virus, and on preventing secondary
transmission by contact tracing and antiviral
medication in an attempt to delay sustained
community transmission. In order to provide a
better basis for the decision whether or not to
initiate preventive measures, expanded testing,
targeting a broad range of respiratory agents has
been applied to specimens from all suspected
cases in the region Vastra Gotaland (1.5 million
inhabitants). We report here the results of this
expanded testing.
Material and methods
This report includes samples of patients who,
during the period from 24 Apr to 10 Jun 2009
presented with influenza-like symptoms and a
history of recent travel to the United States or
Mexico, and therefore were recommended for
examination and sampling. This clinical
examination was performed by infectious disease
clinicians on call at Sahlgrenska University
Hostpital/Östra in Gothenburg, and our report is
based on their evaluation and laboratory results.
In summary, of all 79 patients included with a
travel history, 90 percent presented with
respiratory symptoms, 5 percent without
respiratory symptoms, and for the remaining 5
percent this information is not documented. 66
percent had fever above 38 C, 29 percent had no
fever; information on fever was missing for 5
percent. Nasopharyngeal swabs were sent to the
molecular diagnostic unit at the virological
laboratory at Sahlgrenska University Hospital for
testing by a multiple real-time PCR targeting 13
viruses and 2 bacteria, !
run in 6 parallel multiplex PCRs on an ABI 7500
instrument [6]. Samples that were reactive for
the influenza A component (matrix protein target,
[7]) of this PCR were subtyped by an additional
real-time PCR targeting the haemagglutinin gene,
run in 3 parallel reactions specific for the H3N2
and H1N1 subtypes that have been circulating for
a long time, as well as for the new H1N1v strain.
[Readers requiring information on the primers and
probes used in the real-time PCR are referred to
a Table in the original text].
Results and discussion
In total, samples from 79 patients were tested
(42 males, 37 females; median age 30 years, range
1-75 years), with between 10 and 16 samples on
average each week and most of them taken from
patients with respiratory symptoms and a history
of recent travel to North America. Four cases
with the new influenza A (H1N1)v variant were
diagnosed. Interestingly, in 56 percent of the
cases, other aetiologies were identified (Table).
Table. Viral aetiologies for the patients
fulfilling definition of suspected cases of
influenza A(H1N1)v, Region Vastra Gotaland,
Sweden, Apr-Jun 2009 (n=79)
Viral aetiology / Number / Percentage
Rhinovirus / 28 / 34
Coronavirus / 8 / 10
Influenza B virus / 3 / 4
Human parainfluenza virus types 1-3 / 3 / 3 / 4
Adenovirus / 2 / 2
Influenza A (H1N1) virus / 4 / 5
Metapneumovirus / 1 / 1
Enterovirus / 1 / 1
Respiratory syncytial virus / 0 / 0
Mycoplasma pneumoniae, Chlamydia pneumoniae / 0 / 0
Negative / 32 / 39
Total number / 82 / 100
(Note: 3 patients had double infections with
rhinovirus, together with enterovirus,
metapneumovirus or adenovirus.)
The most common finding was rhinovirus, observed
in 28 of 82 cases (34 percent), and 3 of these
patients also had a 2nd viral infection
(enterovirus, metapneumovirus and adenovirus).
The frequent identification of rhinovirus and
other viruses demonstrates that the criteria for
suspected cases of influenza A(H1N1)v are
relevant as indicators of a viral infection, but
not specific for influenza A. On the other hand,
applying more restrictive criteria would probably
have excluded most infections with the new
A(H1N1) virus strain, considering that their
clinical presentation has been reported to be
relatively mild. This illustrates a dilemma with
surveillance actions aiming at revealing the
spread of new respiratory infections. If the
applied criteria are too strict (for example
fever above 39 C, cough and muscle pain), the
epidemic is likely to be underestimated, because
only the severe cases are identified. If on the
other hand the criteria are liberal, as
illustrated by the cur!
rent epidemic, most of the cases will probably
have other aetiologies. The positive predictive
value of clinical criteria for identification of
influenza A is particularly low in the early
phase of an epidemic, when the incidence of
influenza A is low, but will become relatively
high during the peak when a large proportion of
respiratory infections will be due to influenza A
virus. The value of broad virology testing
decreases in the course of an influenza epidemic,
when the detection rate of other aetiologies may
decrease from above 50 percent as observed in
this report to below 10 percent during the
influenza peak (unpublished observations from our
laboratory).
The cases with influenza A were analysed further
by a typing PCR that within 4-5 hours could
identify whether the strain was a traditional
H1N1 or H3N2 virus, or the new H1N1 variant. This
typing system targets specific regions of the
haemagglutinin gene and has been developed in our
laboratory (unpublished). It has proved to have a
good sensitivity, as illustrated by cycle
threshold (Ct) values that are typically lower
than those obtained in the general PCR for
influenza A, which targets a conserved region of
the matrix protein gene.
The results of the multiple PCR used in our
setting were available within 24 hours after
sampling and served at the same time as
confirmation for the result of the 1st, general
influenza A PCR. In cases that presented with
typical influenza-like symptoms but were negative
for influenza A in the 1st PCR, the finding of an
alternative aetiology was helpful for the
decision to refrain from preventive measures.
Such measures include oseltamivir treatment of
patients and influenza testing and prophylactic
treatment of their close contacts. The clinical
practice was not always different, but in some
cases, the identification of an alternative
aetiology such as rhinovirus was helpful for the
decision not to treat the patient of contacts,
even when the patient had symptoms clearly
indicative of possible influenza. From this
experience, we therefore conclude that a broad
diagnostic test is a valuable tool in the early
investigation of a new emerging respiratory virus
like the new influ!
enza A(H1N1)v.
[Note added in proof: On 17 Jun 2009, Sweden
changed to a stricter case definition for
suspected cases. It now requires more than 2
symptoms besides epidemiology and fever.]
References
1. Centers for Disease Control and Prevention
(CDC). Swine influenza A (H1N1) infection in 2
children--Southern California, Mar-Apr 2009. MMWR
Morb Mortal Wkly Rep. 2009;58(15):400-2.
2. Novel Swine-Origin Influenza A (H1N1) Virus
Investigation Team. Emergence of a Novel
Swine-Origin Influenza A (H1N1) Virus in Humans.
N Engl J Med. 2009 Jun 3. [Epub ahead of print].
3. World Health Organization (WHO). Influenza
A(H1N1) - update 50. Jun 17, 2009. Available from:
<http://www.who.int/csr/don/2009_06_17/en/index.html>.
4. Commission Decision of 30 Apr 2009 amending
Decision 2002/253/ EC laying down case
definitions for reporting communicable diseases
to the Community network under Decision n
21/19/98/EC. 2009/363/EC. Official Journal L
110/58. 01.05.2009. Available from:
<http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2009:110:0058:0059:EN:PDF>.
5. World Health Organization (WHO). Influenza
A(H1N1) - update 2. Apr 26, 2009. Available from:
<http://www.who.int/csr/don/2009_06_17/en/index.html>
6. Brittain-Long R, Nord S, Olofsson S, Westin
J, Anderson LM, Lindh M. Multiplex real-time PCR
for detection of respiratory tract infections. J
Clin Virol. 2008;41(1):53-.
7. Ward CL, Dempsey MH, Ring CJ, Kempson RE,
Zhang L, Gor D, et al. Design and performance
testing of quantitative real time PCR assays for
influenza A and B viral load measurement. J Clin
Virol. 2004;29(3): 179-88.
--
Communicated by:
ProMED-mail <promed@promedmail.org>
[These data among other things reveal that the
positive predictive value of clinical criteria
for identification of influenza A is low in the
early phase of an epidemic, when the incidence of
influenza A is low, but will become relatively
higher during the peak, when a large proportion
of respiratory infections will be due to
influenza A virus. Among the viruses detected,
rhinoviruses and coronaviruses predominated in
this survey. - Mod.CP]
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...................................................cp/msp/lm
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