Human infection with avian influenza A H6N1 virus: an epidemiological analysis

Abstract

Background: Avian influenza A H6N1 virus is one of the most common viruses isolated from wild and domestic avian species, but human infection with this virus has not been previously reported. We report the clinical presentation, contact, and environmental investigations of a patient infected with this virus, and assess the origin and genetic characteristics of the isolated virus.

Methods: A 20-year-old woman with an influenza-like illness presented to a hospital with shortness of breath in May, 2013. An unsubtyped influenza A virus was isolated from her throat-swab specimen and was transferred to the Taiwan Centres for Disease Control (CDC) for identification. The medical records were reviewed to assess the clinical presentation. We did a contact and environmental investigation and collected clinical specimens from the case and symptomatic contacts to test for influenza virus. The genomic sequences of the isolated virus were determined and characterised.

Findings: The unsubtyped influenza A virus was identified as the H6N1 subtype, based on sequences of the genes encoding haemagglutinin and neuraminidase. The source of infection was not established. Sequence analyses showed that this human isolate was highly homologous to chicken H6N1 viruses in Taiwan and had been generated through interclade reassortment. Notably, the virus had a G228S substitution in the haemagglutinin protein that might increase its affinity for the human α2-6 linked sialic acid receptor.

Interpretation: This is the first report of human infection with a wild avian influenza A H6N1 virus. A unique clade of H6N1 viruses with a G228S substitution of haemagglutinin have circulated persistently in poultry in Taiwan. These viruses continue to evolve and accumulate changes, increasing the potential risk of human-to-human transmission. Our report highlights the continuous need for preparedness for a pandemic of unpredictable and complex avian influenza.

Funding: Taiwan Centres for Disease Control.

Figure 1

Chronology of patients Timelines of the patient with H6N1 infection and contacts. The timepoints of illness onset, contact time, and specimen collection are shown by symbols explained in the key.

Figure 2

Chest radiograph of the index patient Chest radiograph taken on May 8 (A), the fourth day of illness, shows increased lung marking and infiltrate in the bilateral lower lung fields. Radiograph taken on May 17 (B) shows the clear lung fields.

Figure 3

Phylogenetic relation of the genes of influenza A H6N1 viruses isolated in Taiwan Phylogenetic relation of the full-length haemagglutinin (A) and neuraminidase (B) genes. The tree was constructed using the neighbour-joining method of MEGA 5.2; the reliability of the trees was assessed by bootstrap analysis with 1000 replications. The H6N1 viruses isolated from chickens in Taiwan comprise a unique lineage and are divided into two clades: 228S with the serine residue at 228 of the haemagglutinin (shown in blue) and 228G with the glycine residue at 228 (shown in red). These colours are used in the phylogenetic trees of the other seven segments. The A/Taiwan/2/2013 in green is the virus isolated from the index patient and the other viruses are from avian species. Phylogenetic trees of the other six segments are shown in the appendix.

Figure 4

Evolutionary histories of influenza H6N1 viruses in Taiwan The genome compositions of the various viruses are based on the phylogenetic topographies in figure 3 and the appendix. The gene segments of the viruses are presented in the order of (from top to bottom) PB2, PB1, PA, HA, NP, NA, M, and NS. Red arrows represent possible evolutionary pathways for PF3/02 virus, green arrows for 0204/05 virus, and blue arrows for A342/05 virus. The red lines show that gene segments possess different mutations. For example, the TW02/13 virus was generated through reassortments among PF3/02 virus, providing the PB1 segment; 0204/05 virus, providing the HA segment; and A342/05 virus, providing the PB2, PA, NP, NA, M, and NS segments. PF3/02=A/chicken/Taiwan/PF3/02. 0204/05=A/chicken/Taiwan/0204/05. A342/05=A/chicken/Taiwan/A342/05. TW02/13=A/Taiwan/2/2013. A2837/13=A/chicken/Taiwan/A2837/2013.