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Archive Number 20090618.2254
Published Date 18-JUN-2009
Subject PRO/AH/EDR> Influenza A (H1N1) - worldwide (69): other viral infections
INFLUENZA A (H1N1) - WORLDWIDE (69): OTHER VIRAL INFECTIONS
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A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

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]

[see also:
Influenza A (H1N1) - worldwide (68): southern hemisphere (to be archived)
Influenza A (H1N1) - worldwide (67): comments on 1918 virus 20090618.2251
Influenza A (H1N1) - worldwide (66): new strain, 
sequence analysis 20090617.2235
Influenza A (H1N1) - worldwide (65): antivirals in pregnancy 20090616.2224
Influenza A (H1N1) - worldwide (64): case count, pandemic 20090616.2221
Influenza A (H1N1) - worldwide (63): case count, pandemic 20090611.2166
Influenza A (H1N1) - worldwide (62): Egypt, Lebanon 20090611.2150
Influenza A (H1N1) - worldwide (60): Egypt (Cairo) 20090608.2117
Influenza A (H1N1) - worldwide (59): Worldwide 20060608.2117
Influenza A (H1N1) - worldwide (58): USA, Africa 20090607.2109
Influenza A (H1N1) - worldwide (57): Brazil, USA 20090605.2090
Influenza A (H1N1) - worldwide (56): case counts 20090605.2089
Influenza A (H1N1) - worldwide (55) 20090603.2056
Influenza A (H1N1) - worldwide (54): dynamics 20090601.2038
Influenza A (H1N1) - worldwide (53): case counts 20090531.2025
Influenza A (H1N1) - worldwide (52): seasonal vaccine 20090530.2010
Influenza A (H1N1) - worldwide (51): dynamics 20090529.1999
Influenza A (H1N1) - worldwide (50): swine immunity 20090528.1987
Influenza A (H1N1) - worldwide (49): case counts 20090528.1984
Influenza A (H1N1) - worldwide (48): case counts 20090527.1972
Influenza A (H1N1) - worldwide (47): China, epidemiology 20090526.1962
Influenza A (H1N1) - worldwide (46): case counts 20090526.1960
Influenza A (H1N1) - worldwide (45) 20090525.1951
Influenza A (H1N1) - worldwide (44): case counts 20090525.1945
Influenza A (H1N1) - worldwide (43): case counts 20090523.1931
Influenza A (H1N1) - worldwide (42) 20090523.1929
Influenza A (H1N1) - worldwide (41): case counts 20090522.1921
Influenza A (H1N1) - worldwide (40): case counts 20090521.1906
Influenza A (H1N1) - worldwide (39) 20090521.1903
Influenza A (H1N1) - worldwide (38): case counts 20090520.1895
Influenza A (H1N1) - worldwide (37) 20090520.1893
Influenza A (H1N1) - worldwide (36): case counts, amended 20090519.1882
Influenza A (H1N1) - worldwide (35): case counts 20090518.1867
Influenza A (H1N1) - worldwide (34) 20090518.1863
Influenza A (H1N1) - worldwide (33): case counts 20090517.1848
Influenza A (H1N1) - worldwide (32): case counts 20090517.1845
Influenza A (H1N1) - worldwide (31) 20090516.1835
Influenza A (H1N1) - worldwide (30): case counts 20090516.1831
Influenza A (H1N1) - worldwide (29) 20090515.1824
Influenza A (H1N1) - worldwide (28): case counts 20090515.1822
Influenza A (H1N1) - worldwide (27): case counts 20090514.1800
Influenza A (H1N1) - worldwide (26) 20090514.1798
Influenza A (H1N1) - worldwide (25): case counts 20090513.1785
Influenza A (H1N1) - worldwide (24): case counts 20090512.1772
Influenza A (H1N1) - worldwide (23) 20090511.1764
Influenza A (H1N1) - worldwide (22): case counts 20090511.1759
Influenza A (H1N1) - worldwide (21) 20090510.1749
Influenza A (H1N1) - worldwide (20): case counts 20090510.1741
Influenza A (H1N1) - worldwide (19) 20090509.1733
Influenza A (H1N1) - worldwide (18): case counts 20090509.1728
Influenza A (H1N1) - worldwide (17) 20090508.1722
Influenza A (H1N1) - worldwide (16): case counts 20090507.1715
Influenza A (H1N1) - worldwide (15) 20090507.1709
Influenza A (H1N1) - worldwide (14): case counts 20090507.1702
Influenza A (H1N1) - worldwide (13) 20090506.1695
Influenza A (H1N1) - worldwide (12): case counts 20090505.1681
Influenza A (H1N1) - worldwide (11): coincident H3N2 variation 20090505.1679
Influenza A (H1N1) - worldwide (10): case counts 20090504.1675
Influenza A (H1N1) - worldwide (09) 20090504.1673
Influenza A (H1N1) - worldwide (08): case counts 20090503.1660
Influenza A (H1N1) - worldwide (07) 20090503.1658
Influenza A (H1N1) - worldwide (06): case counts 20090502.1654
Influenza A (H1N1) - worldwide (05) 20090503.1657
Influenza A (H1N1) - worldwide (04): case counts 20090501.1648
Influenza A (H1N1) - worldwide (03) 20090501.1646
Influenza A (H1N1) - worldwide (02): case counts 20090430.1638
Influenza A (H1N1) - worldwide 20090430.1636
Influenza A (H1N1) "swine flu": worldwide (07), 
update, pandemic 5 20090429.1622
Influenza A (H1N1) "swine flu": worldwide (06) 20090429.1614
Influenza A (H1N1) "swine flu": worldwide (05) 20090428.1609
Influenza A (H1N1) "swine flu": worldwide (04) 20090428.1601
Influenza A (H1N1) "swine flu": worldwide (03) 20090428.1600
Influenza A (H1N1) "swine flu": Worldwide (02) 20090427.1586
Influenza A (H1N1) "swine flu": Worldwide 20090427.1583
Influenza A (H1N1) virus, human: worldwide 20090426.1577
Influenza A (H1N1) virus, human - New Zealand, susp 20090426.1574
Influenza A (H1N1) virus, human - N America (04) 20090426.1569
Influenza A (H1N1) virus, human - N America (03) 20090426.1566
Influenza A (H1N1) virus, human - N America (02) 20090425.1557
Influenza A (H1N1) virus, human - N America 20090425.1552
Acute respiratory disease - Mexico, swine virus susp 20090424.1546
Influenza A (H1N1) virus, swine, human - USA (02): (CA, TX) 20090424.1541
Influenza A (H1N1) virus, swine, human - USA: (CA) 20090422.1516
Influenza A (H1N1) virus, swine, human - Spain 20090220.0715
2008
----
Influenza A (H1N1) virus, swine, human - USA (TX) 20081125.3715
2007
----
Influenza A (H2N3) virus, swine - USA 20071219.4079
Influenza, swine, human - USA (IA): November 2006 20070108.0077]
...................................................cp/msp/lm

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