Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004.

The 2004 outbreaks of H5N1 influenza viruses in Vietnam and Thailand were highly lethal to humans and to poultry; therefore, newly emerging avian influenza A viruses pose a continued threat, not only to avian species but also to humans. We studied the pathogenicity of four human and nine avian H5N1/04 influenza viruses in ferrets (an excellent model for influenza studies). All four human isolates were fatal to intranasally inoculated ferrets. The human isolate A/Vietnam/1203/04 (H5N1) was the most pathogenic isolate; the severity of disease was associated with a broad tissue tropism and high virus titers in multiple organs, including the brain. High fever, weight loss, anorexia, extreme lethargy, and diarrhea were observed. Two avian H5N1/04 isolates were as pathogenic as the human viruses, causing lethal systemic infections in ferrets. Seven of nine H5N1/04 viruses isolated from avian species caused mild infections, with virus replication restricted to the upper respiratory tract. All chicken isolates were nonlethal to ferrets. A sequence analysis revealed polybasic amino acids in the hemagglutinin connecting peptides of all H5N1/04 viruses, indicating that multiple molecular differences in other genes are important for a high level of virulence. Interestingly, the human A/Vietnam/1203/04 isolate had a lysine substitution at position 627 of PB2 and had one to eight amino acid changes in all gene products except that of the M1 gene, unlike the A/chicken/Vietnam/C58/04 and A/quail/Vietnam/36/04 viruses. Our results indicate that viruses that are lethal to mammals are circulating among birds in Asia and suggest that pathogenicity in ferrets, and perhaps humans, reflects a complex combination of different residues rather than a single amino acid difference.

Prevalence and incidence of Chlamydia pneumoniae antibodies among the healthy elderly and patients with chronic obstructive pulmonary diseases.

Chlamydia pneumoniae is an obligatory intracellular bacteria which can cause both acute and chronic respiratory tract infection. The significance of chronic and recurrent respiratory infection may be of prime importance in chronic obstructive pulmonary diseases (COPD). The purpose of this study was to determine the prevalence and incidence of C. pneumoniae antibodies in elderly COPD patients compared to a healthy elderly control group. C. pneumoniae antibodies were detected by an enzyme-linked immunosorbent assay in serum samples obtained from 127 elderly COPD patients and a 131 healthy elderly control group. The results showed that the seroprevalence of C. pneumoniae infection as determined by the existence of specific IgG or IgA or IgM antibodies was 96.1% in the COPD patients and 75.6% in the control group (p < 0.01). The prevalence of individual C. pneumoniae IgG, IgA and IgM in elderly COPD vs healthy control was 85.8% vs 66.4%, 85.0% vs 51.1% and 3.9% vs 0%, respectively. The incidence or seroconversion rate of C. pneumoniae antibodies after one year follow-up was found to be 33% in the COPD patients and 67.9% in the control group. High prevalence and incidence of C. pneumoniae antibodies indicates that both acute and chronic C. pneumoniae infection play a role in elderly COPD patients. Therefore, antibiotics of choice for C. pneumoniae infection should probably be considered.