Haemophilus influenzae type B meningitis among children in Hanoi, Vietnam: epidemiologic patterns and estimates of H. Influenzae type B disease burden.

From March 2000 to February 2002, a population-based study of Haemophilus influenzae type b (Hib) meningitis was conducted among children less than five years of age in Hanoi, Vietnam. Children with suspected bacterial meningitis were referred to hospitals and each patient underwent standardized clinical examination and microbiologic testing. In Hanoi, 580 children were evaluated for bacterial meningitis and 23 (4%) had confirmed or probable Hib meningitis. The incidence of all Hib meningitis was 12/100,000 child-years less than five years of age and 26/100,000 child-years less than two years of age. Nationally, an estimated 1,005 children less than five years of age are hospitalized for Hib meningitis and 5,107 are hospitalized for Hib pneumonia. Among children with Hib meningitis, at least 100 will develop severe neurologic sequelae and 40 will die. These data suggest there is a substantial burden of Hib disease in Vietnam. National leaders will be provided with these data to facilitate development of national vaccination policies for children in Vietnam.

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.