Update on human infections with highly pathogenic avian influenza
virus A/H7N7 during an outbreak in poultry in the Netherlands
1 Diagnostic Laboratory for Infectious Diseases and Perinatal
Screening, National Institute of Public Health and the Environment (RIVM),
Bilthoven, The Netherlands.
2 Department of Virology, Erasmus Medical Center Rotterdam, Rotterdam, The
3 Municipal Health Service Gelderland Midden, Arnhem, The Netherlands.
4 National Co-ordination Center for Communicable Disease Control, Utrecht,
5 European Programme for Intervention Epidemiology Training (EPIET)
6 Department of Infectious Diseases Epidemiology, RIVM, Bilthoven, The Netherlands.
During the 2003 outbreak of avian influenza caused by highly pathogenic
avian influenza (HPAI) virus A/H7N7 in the Netherlands, human infection
with this virus occurred in unexpectedly high numbers. The first signs of
human infection were found in a veterinarian who visited several farms with
infected poultry and subsequently developed acute conjunctivitis caused
by the A/H7N7 virus. Human influenza virus (mostly A/H3N2) was circulating
in the community simultaneously. In view of the potential risk of co-infection
and reassortment, active case finding among people exposed to infected poultry
was implemented immediately.
A case of conjunctivitis was defined as a person who had been exposed to
contaminated poultry or a confirmed human case of avian influenza A/H7 since
28 February in the Netherlands, with at least two of the following symptoms:
flow of tears or red or itching or painful or burning eyes or pus or photophobia.
A case of influenza-like illness (ILI) was defined as a person who had been
exposed to contaminated poultry or a confirmed human case of avian influenza
A/H7 since 28 February in the Netherlands with acute illness onset and fever
with at least one of the following symptoms: cough, rhinorrhoea, sore throat,
myalgia, or headache. Based on the initial findings, all those involved
in the culling of poultry were advised to wear protective goggles and face
masks, and to wash their hands, especially before returning home from work.
In addition, vaccination with the current influenza vaccine and prophylactic
treatment with neuraminidase inhibitors of all people exposed to infected
poultry was initiated, as well as treatment of all patients reporting to
the municipal health services who had been exposed.
As of 22 April, conjunctival and throat swabs were collected from 293 patients,
of whom 260 fitted the case definition of conjunctivitis and/or ILI (see
table 1). Seventy eight of 260 cases had H7 positive conjunctival swabs.
Eight cases also had an H7 positive throat swab. One had an H7 positive
throat swab only. One of the cases presenting with ILI only had an H7 positive
conjunctival swab. An additional two patients who did not fit the case definition
for conjunctivitis had H7 positive lab results. Both complained of 'burning
eyes' only. Six cases had H3 positive throat swabs, but no simultaneous
infection with H7 and H3 influenza virus was detected.
Most conjunctivitis cases occurred between 5 and 20 March, after which
date the number of new cases dropped below five reports per day (figure
1). This was approximately five days after implementation of the more stringent
precautionary measures, including prophylactic treatment with oseltamivir
of all persons exposed to suspected or confirmed infected poultry. Two weeks
later, however, the number of reported and confirmed cases showed a slight
increase. Only eight of 25 new cases (32%) claim to have taken oseltamivir
prophylaxis in accordance with the guidelines, although all have had prolonged
exposure to suspect or confirmed infected poultry. A relevant finding was
also the confirmation of A/H7 associated conjunctivitis in four poultry
workers from Poland and one from Belgium, all involved in the culling. While
the risk is low, they do present a possible vector for transmission of avian
influenza virus to other areas. This finding was communicated to the health
authorities in Poland, Germany, and Belgium.
There has been preventive depopulation of poultry flocks in Germany along
the border with the Netherlands, although there have so far been no suspected
or confirmed AI infections in German poultry. Precautionary measures regarding
possible spread of the virus to other farms and among humans are being implemented.
Three household contacts of confirmed cases developed A/H7-associated conjunctivitis
while they had no direct exposure to infected poultry. All three had conjunctivitis
as the most prominent presenting symptom, while one (a 12 year old child)
additionally developed ILI. These results strongly suggest person to person
transmission of avian influenza A/H7N7 virus.
On April 17, a veterinarian who had visited a poultry farm infected with
HPAI died as the result of acute respiratory distress syndrome, which developed
following a one week episode of ILI. Conjunctivitis was not observed, and
the course of illness was protracted with bilateral pneumonia unresponsive
to treatment resulting in death two weeks later. The veterinarian had visited
an infected flock for sampling, and was not taking prophylactic drugs for
reasons that have not yet been clarified. There was no history of underlying
illness. The diagnostic evaluation was complicated: throat and conjunctival
samples collected after one week of illness tested negative for A/H7 in
both labs involved in the testing. A bronchoalveolar lavage collected two
days later was positive for A/H7. Differential diagnostic tests for legionella,
mycoplasma, psittacosis and other bacterial pathogens were negative. All
hospital contacts and the relatives of this person were given oseltamivir
prophylaxis, and persons with symptoms were sampled for virological testing.
So far no secondary transmissions have been detected.
Release of information about the death to the media resulted in an upsurge
of reports of possible cases, and renewed discussion about the detail of
the preventive measures. It was reinforced that poultry workers and farmers,
including anyone visiting an infected flock, should wear protective clothing,
masks to cover the mouth and nose, and eye protection, be vaccinated against
influenza, and have prophylactic antiviral medication. Based on the existing
information, the consensus is that these measures should prevent serious
consequences of A/H7 transmission.
At present, a cohort study is being conducted among confirmed cases and
their household contacts in order to ascertain the extent of person to person
transmission of AI and to identify risk factors. Another cohort study among
poultry workers and poultry farmers will be conducted, in order to study
risk factors for transmission of AI from poultry to humans.
Our preliminary observations support the hypothesis that infected humans
might function as a 'mixing vessel' for generating novel influenza viruses
and strongly support a need for active surveillance and pandemic planning.
Table 1: Results of laboratory testing in cases of conjunctivitis,
Influenza Like Illness (ILI) and other patients who had been exposed to
suspected or confirmed AI infected poultry in The Netherlands.
||Conjunctivitis and ILI
|Positive (not yet typed)
|No samples available
Figure 1: Human cases of conjunctivitis after exposure
to avian influenza A/H7 in the Netherlands according to date of onset and