Management of potential human cases of influenza A/H5N1: lessons
Since the first human cases of influenza A/H5N1 were widely
reported from Turkey in early January, many European patients with suspected
influenza, who might have been exposed to influenza A/H5N1 in countries reporting
human or avian cases, have been tested for the infection. The 28 countries
participating in the European Influenza Surveillance Scheme (EISS, http://www.eiss.org
have been invited to report any laboratory tests for H5N1, and by 25 January,
six countries had reported a total of 19 tests [personal communication, A
Meijer, 25 January 2006]. This small number of tests – all of which were negative
– probably represents only a small proportion of the suspect cases of influenza
A/H5N1 that have been treated in Europe in recent weeks. We present here Belgium’s
experience in managing its first suspected human case of influenza A/H5N1.
On 13 January 2006, a Russian journalist presented at the emergency department
of a Brussels hospital with high fever, muscle pain, general discomfort,
cough, nasal discharge and sore throat. He had visited poultry farms in
the eastern province of Van, Turkey, from 9 to 12 January, while making
a documentary film about avian influenza.
According to the standard operational procedures (SOP) for the management
of a potential case of human A/H5N1 in Belgium, the hospital reported the
case to the Health Inspectorate of Brussels and the Scientific Institute
of Public Health (IPH) in Brussels. After epidemiological evaluation, the
patient was classified as a probable case* because he had visited poultry
farms in an area affected by avian influenza . In accordance with the
SOP, nasopharyngeal swabs were taken, using the sampling material and the
protection equipment that had been sent to all the clinical laboratories
in Belgium as a preparedness measure . The specimens were immediately
sent to the National Influenza Centre at the IPH for testing. In line with
recommendations for the management of probable cases, the patient was transferred
to the Saint-Pierre referral hospital in Brussels for immediate isolation.
He received a presumptive treatment of oseltamivir 150 mg bid and specific
protective measures were applied.
As soon as the case was notified, a list was made of all people who could
potentially have been exposed to avian influenza. These included those who
were exposed to the same risk as the patient, or had had recent contact
with the patient. The cameraman who had also been working on the documentary
film in Turkey was considered to have been exposed. Household contacts and
healthcare workers who had been in contact with the patient without wearing
protective equipment at the first hospital, before he was considered to
be a potential case of A/H5N1, were informed. The cameraman and the household
contacts did not report any flu-like symptoms.
Passengers who had travelled on the three connecting flights taken by the
patient between Turkey and Belgium were also considered to be contacts.
Investigators attempted to obtain passenger lists so that the passengers
could be contacted if the case was confirmed, but the airline companies
refused to disclose the names of the passengers, citing the need to protect
The nasopharyngeal swabs were processed in a biosafety level 3 laboratory
with a rapid enzyme immunoassay test (EIA) and with subsequent RNA extraction.
RNA was subjected to two real time PCR (typing A and subtyping H5) and four
nested RT-PCR tests (typing A and B, subtyping H5, subtyping H3 and H1,
subtyping N1 and N2). The specimen was positive for influenza A using real
time PCR, nested RT-PCR and the less sensitive EIA test. H5 subtyping was
negative using both real-time and nested RT-PCR. Further subtyping using
nested RT-PCR identified a human influenza A/H3N2 infection. Preliminary
laboratory results were available one hour (EIA) and four hours (real time
PCR) after receiving the specimens. Confirmation results from the nested
RT-PCR tests were reported to the public health authorities after 16 hours
(the time taken for A and B typing, and H5, H3 and H1 subtyping) and 36
hours (the time taken for N1 and N2 subtyping).
These laboratory results allowed investigators to discard the possibility
of an A/H5N1 infection, and showed that the patient was the first case of
influenza A/H3N2 infection in Belgium to be identified by the National Influenza
Centre during the 2005-2006 season. During the first week of 2006, clinical
influenza activity in Belgium was very low, as in most European countries
Precautionary measures were discontinued when the final confirmation of
A/H3N2 was made on 15 January. The patient left the hospital on the same
day, without fever and in good general health.
Information on seasonal influenza from Turkey is scarce, but influenza
activity is reported to be low . Taking into account the influenza incubation
period, it is not possible to determine whether the patient was infected
in Turkey or in Belgium, before beginning his journey.
This incident raises the question of whether travellers to areas affected
by avian A/H5N1 influenza should be advised to receive the seasonal influenza
vaccination during the influenza season.
This case has demonstrated that the Belgian case definition for suspect
avian influenza A/H5N1 is capable of detecting influenza. The SOP for the
management of suspect cases of human A/H5N1 case in Belgium, validated by
health authorities and communicated to health professionals in late 2005,
were appropriately and rapidly applied.
International guidelines are needed on the management of international
flight passengers who have been in contact with a confirmed A/H5N1 case.
Coordination is also needed at international level to facilitate the process
of tracing passengers.
*Belgian case definitions for categories of avian influenza A/H5N1
cases, phase 3 (WHO), updated November 2005 :
||Possible case: any individual with fever (>38°C)
and cough and general discomfort, who has been in closed contact during
the seven days before the onset of symptoms with wild or domestic birds,
live or dead, or with their droppings, in a country affected by avian
||Probable case: possible case with preliminary positive
laboratory results for avian flu, or with respiratory distress/death
for which an alternative diagnosis has not been established, or with
a highly suggestive epidemiological context evaluated by experts.
||Confirmed case: Positive PCR for A/H5N1, or virus
isolation by culture, or a fourfold increase of specific H5 antibodies.
We would like to thank Dr Y Vandeput and the staff of the emergency department
at the Clinique Sainte Elisabeth in Brussels who alerted health authorities
and took the first measures, as well as the staff of the Hôpital Saint-Pierre,
for their work.