Published Date: 2003-03-19 23:50:00
Subject: PRO/AH/EDR> Avian Influenza, human - Netherlands (07)
Archive Number: 20030319.0687
AVIAN INFLUENZA, HUMAN - NETHERLANDS (07)
A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases
Date: Wed 19 Mar 2003
From: Adam Meijer <Adam.Meijer@rivm.nl>
The antiviral susceptibility of the highly pathogenic avian influenza
(HPAI) H7N7 influenza A virus causing conjunctivitis in humans
Following the identification of an increasing number of human cases of
influenza A/H7N7 associated conjunctivitis last week, we determined the
susceptibility of the virus isolated from the clinical sample of the first
reported case in anticipation of the possible use of antivirals for the
prophylaxis and treatment of HPAI H7N7 (1). This stock virus was typed as
H7 using the hemagglutination inhibition assay with an anti-H7 antiserum.
The susceptibility of the virus for the neuraminidase inhibitors
oseltamivir (Tamiflu) and zanamivir (Relenza) was tested using a
miniaturized format of the fetuin based biochemical assay (2). [Oseltamivir
and zanamivir are a well-tolerated influenza virus neuraminidase
inhibitors, active against both A and B influenza viruses. Oseltamivir is
administered orally, and zanamivir via an inhaler. - Mod.CP].
The 50 per cent inhibitory concentration (IC50) of oseltamivir for the H7N7
virus was 1.29 nM (95 per cent confidence interval [CI] 1.19-1.40 nM) and
of zanamivir 3.94 nM (CI 3.61-4.29). A known sensitive control virus
(A/Chicken/Pennsylvania/21525/83 H5N2) had an IC50 of 0.33 nM (CI
0.30-0.36) for oseltamivir, similar to previous observations. IC50 values
for sensitive H1N1 and H3N2 clinical isolates were between 0.2 and 6.8 nM
for oseltamivir and between 0.3 and 13.1 nM for zanamivir, dependent on
isolate and assay (3).
This shows that the currently circulating HPAI H7N7 virus in the
Netherlands is susceptible to oseltamivir as well as zanamivir. Since
orally dosed oseltamivir becomes available systemically (highly likely
including the conjunctivae via the tear-fluid) whereas zanamivir taken via
an inhalator is only locally active in the respiratory tract, Tamiflu was
the drug of choice for the prophylaxis and treatment of infection of
persons with the H7N7 virus (4).
These measures, effective as of 16 Mar 2003, call for prophylactic
oseltamivir treatment of all persons involved directly in the screening and
culling of infected flocks, and therapeutic application in all persons
within these groups with conjunctivitis and/or influenza-like illness. [The
rationale is presumably to reduce the probability of co-infection of
individuals by the avian virus and any fortuitously circulating human
influenza virus, which might allow the generation by sub-unit reassortment
of a human influenza A virus with a novel combination of haemagglutinin (H)
and neuraminidase (N) antigens. - Mod.CP].
(1) Fouchier R, Koopmans M, Meijer A, Wilbrink B, van Wijngaarden J,
Osterhaus A. Avian Influenza, human - Netherlands. H7N7 Conjunctivitis;
human. ProMED-mail posting, 11 Mar 2003. [see: "Avian influenza, human -
Netherlands 20030311.0594"] .
(2) Aymard-Henry, et al. Bull World Health Org 1973; 48: 199-202.
(3) Wetherall, et al. J Clin Microbiol 2003; 742-50.
(4) Ministry of Health, Welfare and Sport, The Netherlands. Extra
maatregelen tegen risico's vogelpestvirus (press release) 15 Mar 2003.
(<http://www.minvws.nl/document.html?folder=393&page=19369>) [see: "Avian
influenza, human - Netherlands (04) 20030315.0643"].
Contributed by Adam Meijer, Berry Wilbrink, Jan van Wijngaarden, Ron
Fouchier, Ab Osterhaus, Marion Koopmans, National Institute of Public
Health and the Environment, Bilthoven, The Netherlands. (Jan van
Wijngaarden is inspector of infectious diseases of the Ministry of Health,
Welfare and Sport; Ron Fouchier and Ab Osterhaus are from the National
Influenza Centre for the WHO in the Netherlands at Erasmus MC, Rotterdam,
Adam Meijer, PhD
Diagnostic Laboratory for Infectious Diseases and Perinatal Screening
National Institute of Public Health and the Environment
PO Box 1, 3720 BA Bilthoven
[ProMED-mail welcomes the opportunity to assist in disseminating this
essential information rapidly to interested parties. ProMED-mail has no
commercial association with the biopharmaceutical companies marketing these
neuraminidase inhibitors. - Mod.CP]