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Case Reports
, 101 (5), 1356-61

Avian Influenza A Virus (H7N7) Associated With Human Conjunctivitis and a Fatal Case of Acute Respiratory Distress Syndrome

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Case Reports

Avian Influenza A Virus (H7N7) Associated With Human Conjunctivitis and a Fatal Case of Acute Respiratory Distress Syndrome

Ron A M Fouchier et al. Proc Natl Acad Sci U S A.

Abstract

Highly pathogenic avian influenza A viruses of subtypes H5 and H7 are the causative agents of fowl plague in poultry. Influenza A viruses of subtype H5N1 also caused severe respiratory disease in humans in Hong Kong in 1997 and 2003, including at least seven fatal cases, posing a serious human pandemic threat. Between the end of February and the end of May 2003, a fowl plague outbreak occurred in The Netherlands. A highly pathogenic avian influenza A virus of subtype H7N7, closely related to low pathogenic virus isolates obtained from wild ducks, was isolated from chickens. The same virus was detected subsequently in 86 humans who handled affected poultry and in three of their family members. Of these 89 patients, 78 presented with conjunctivitis, 5 presented with conjunctivitis and influenza-like illness, 2 presented with influenza-like illness, and 4 did not fit the case definitions. Influenza-like illnesses were generally mild, but a fatal case of pneumonia in combination with acute respiratory distress syndrome occurred also. Most virus isolates obtained from humans, including probable secondary cases, had not accumulated significant mutations. However, the virus isolated from the fatal case displayed 14 amino acid substitutions, some of which may be associated with enhanced disease in this case. Because H7N7 viruses have caused disease in mammals, including horses, seals, and humans, on several occasions in the past, they may be unusual in their zoonotic potential and, thus, form a pandemic threat to humans.

Figures

Fig. 1.
Fig. 1.
Amino acid sequence alignment of the HA ORFs of selected isolates. The HA genes of A/Mallard/Netherlands/12/00 (H7N3), A/Chicken/Netherlands/1/03 (H7N7), and A/Netherlands/219/03 (H7N7) are shown. The sequence of the chicken isolate is identical to that of A/Netherlands/33/02 (H7N7). Gaps are indicated by dashes, and identical residues to the mallard isolate are indicated by periods. Boxes indicate the potential N-linked glycosylation sites (N-X-T/S), and the shaded residues represent the cleavage site in the HA precursor protein.
Fig. 2.
Fig. 2.
Amino acid sequence alignment of the NA ORFs of selected isolates. The NA genes of A/Mallard/Netherlands/2/00 (H10N7), A/Chicken/Netherlands/1/03 (H7N7), and A/Netherlands/219/03 (H7N7) are shown. The sequence of the chicken isolate is identical to that of A/Netherlands/33/02 (H7N7). Gaps are indicated by dashes, and identical residues to the mallard isolate are indicated by periods. Boxes indicate the potential N-linked glycosylation sites (N-X-T/S).
Fig. 3.
Fig. 3.
Detection of H7N7 influenza A virus in humans. (A) Numbers of confirmed cases of H7N7 infection in individuals presenting with conjunctivitis or influenza-like illness in The Netherlands between March 1 and April 30, 2003, as determined by RT-PCR. (B) Comparison of the Ct values, the first TaqMan RT-PCR cycle in which matrix gene of influenza A virus was detected in throat/nose (open bars) or conjunctiva (filled bars) swabs in H7N7 and H3N2 influenza A virus-infected individuals, identified in the same group of individuals in the same time period.
Fig. 4.
Fig. 4.
Chest x-ray taken on admission on April 9, 2003, of the veterinarian who developed acute respiratory distress syndrome and died on April 17, 2003. The x-ray reveals extensive infiltrates in the lower right lobe without pleural effusion. The left lung is normal. The label (L) indicates the point of reference on the upper left arm.
Fig. 5.
Fig. 5.
Phylogenetic trees representing the internal genes of influenza A viruses. Trees were constructed based on a 2,302-nt fragment of gene segment 1 (PB2), a 2,285-nt fragment of gene segment 2 (PB1), a 2,151-nt fragment of gene segment 3 (PA), a 1,498-nt fragment of gene segment 5 (NP), a 979-nt fragment of gene segment 7 (MA), and a 885-nt fragment of gene segment 8 (NS). Sequences obtained from influenza virus A/Chicken/Netherlands/1/03 were aligned with those of reference strains available from GenBank, representing the known genetic lineages of influenza A virus. Scale bars represent ≈10% of nucleotide changes between close relatives.

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