Strategies for Early Vaccination During Novel Influenza Outbreaks.

Ongoing research and technology developments hold the promise of rapid production and large-scale deployment of strain-specific or cross-protective vaccines for novel influenza viruses. We sought to investigate the impact of early vaccination on age-specific attack rates and evaluate the outcomes of different vaccination strategies that are influenced by the level of single or two-dose vaccine-induced protections. We developed and parameterized an agent-based model for two population demographics of urban and remote areas in Canada. Our results demonstrate that there is a time period before and after the onset of epidemic, during which the outcomes of vaccination strategies may differ significantly and are highly influenced by demographic characteristics. For the urban population, attack rates were lowest for children younger than 5 years of age in all vaccination strategies. However, for the remote population, the lowest attack rates were obtained for adults older than 50 years of age in most strategies. We found that the reduction of attack rates following the start of vaccination campaigns during the epidemic depends critically on the disease transmissibility, suggesting that for a sufficiently high transmissibility, vaccine delivery after the onset of epidemic has little or no effect, regardless of the population demographics.

Streptococcus suis serotype 2 interactions with human brain microvascular endothelial cells.

Streptococcus suis serotype 2 is a worldwide causative agent of many forms of swine infection and is also recognized as a zoonotic agent causing human disease, including meningitis. The pathogenesis of S. suis infections is poorly understood. Bacteria circulate in the bloodstream in the nonimmune host until they come in contact with brain microvascular endothelial cells (BMEC) forming the blood-brain barrier. The bacterial polysaccharide capsule confers antiphagocytic properties. It is known that group B streptococci (GBS) invade and damage BMEC, which may be a primary step in the pathogenesis of neonatal meningitis. Interactions between S. suis and human endothelial cells were studied to determine if they differ from those between GBS and endothelial cells. Invasion assays performed with BMEC and human umbilical vein endothelial cells demonstrated that unlike GBS, S. suis serotype 2 could not invade either type of cell. Adherence assays showed that S. suis adhered only to BMEC, whereas GBS adhered to both types of cell. These interactions were not affected by the presence of a capsule, since acapsular mutants from both bacterial species adhered similarly compared to the wild-type strains. Lactate dehydrogenase release measurements indicated that some S. suis strains were highly cytotoxic for BMEC, even more than GBS, whereas others were not toxic at all. Cell damage was related to suilysin (S. suis hemolysin) production, since only suilysin-producing strains were cytotoxic and cytotoxicity could be inhibited by cholesterol and antisuilysin antibodies. It is possible that hemolysin-positive S. suis strains use adherence and suilysin-induced BMEC injury, as opposed to direct cellular invasion, to proceed from the circulation to the central nervous system.

Role of capsular sialic acid in virulence and resistance to phagocytosis of Streptococcus suis capsular type 2.

Streptococcus suis capsular type 2 has a capsule rich in sialic acid (NANA). Sialic acid, known to be an antiphagocytic factor for many bacterial species, inhibits the activation of the alternative complement pathway. The role of capsular NANA in virulence, resistance to phagocytosis and intracellular survival of S. suis capsular type 2 was evaluated. In general, a low concentration of NANA was observed for all the S. suis strains tested. In addition, no difference could be found in NANA concentrations between strains of different virulence degrees. Sialic acid concentration increased in the virulent strain 89-1591 and the avirulent strain 90-1330 after in vivo growth with an increased capsular material thickness compared to growth in vitro. No significant difference could be found in the phagocytosis rate by porcine blood monocytes of either strain and strain 89-1591 treated with sialidase or the sialic acid-binding lectin from Sambucus nigra (SNA I). Intracellular survival of strain 89-1591 decreased after treatments with sialidase or lectin, becoming comparable to that of strain 90-1330. Finally, no difference could be seen in virulence using a murine model, even if strain 89-1591 was treated with the enzyme or the lectin. Thus, NANA does not seem to be a critical virulence factor for S. suis capsular type 2.

Streptococcus pneumoniae types 19A and 19F and Streptococcus suis capsular type 8 share common capsular epitopes.

Two monoclonal antibodies (MAbs) to Streptococcus pneumoniae types 19A and 19F were tested with the 35 reference strains and 334 field strains of Streptococcus suis by dot blotting. Both MAbs reacted with the capsular type 8 reference strain, and one reacted with 69% and one reacted with 100% of 81 S. suis capsular type 8 field strains tested. Epitopes recognized by both MAbs are capsular in origin.

Agglutination of Streptococcus suis by sialic acid-binding lectins.

The 35 Streptococcus suis capsular-type reference strains as well as 45 field strains of type 2 were tested with sialic acid-binding lectins from Sambucus nigra (SNA I), Triticum vulgaris, Maackia amurensis, Homarus americanus, and Limax flavus. Only types 1, 1/2, 2, 14, 15, and 16 agglutinated with SNA I and/or the T. vulgaris lectin. All field strains agglutinated only with SNA I. Reaction with SNA I was probably due to the sialic acid moiety since it disappeared after sialidase treatment. These results confirm the presence of sialic acid in S. suis with the possible terminal sequence N-acetylneuraminic acid-alpha(2,6)GalNAc.

Contact-dependent acquisition of transferrin-bound iron by two strains of Haemophilus parasuis.

Two strains of Haemophilus parasuis, namely, the type strain (ATCC 19417) and strain E751, were investigated with respect to iron acquisition. Both strains produced iron-repressible outer membrane proteins and could acquire iron from porcine transferrin but not from porcine lactoferrin. Neither strain used bovine transferrin, and human transferrin was used to only a very limited extent, if at all. In all cases, iron acquisition from transferrin required direct contact between the organisms and the protein. An affinity isolation technique based on biotinylated porcine transferrin plus streptavidin-agarose, followed by SDS-PAGE, allowed the isolation and identification of two potential porcine transferrin binding polypeptides (94 and 60 kDa) from total membranes derived from the type strain grown under iron-restricted conditions but only one (96 kDa) from strain E751. Each of these polypeptides was iron repressible and was not isolated when biotinylated human or bovine transferrin was used instead of biotinylated porcine transferrin. It is concluded that both strains acquire transferrin-bound iron by means of siderophore-independent mechanisms and that the isolated polypeptides represent porcine transferrin receptor components.

Evaluation of a saline boiled extract, capsular polysaccharides and long-chain lipopolysaccharides of Actinobacillus pleuropneumoniae serotype 1 as antigens for the serodiagnosis of swine pleuropneumonia.

A saline boiled extract (SBE), capsular polysaccharides (CPS) and long-chain lipopolysaccharides (LC-LPS) of Actinobacillus pleuropneumoniae serotype 1 have been evaluated in ELISA for the serodiagnosis of swine pleuropneumonia caused by this serotype. Mean optical densities (ODs) obtained with the three antigens using sera from negative herds as well as from animals experimentally and naturally exposed to A. pleuropneumoniae serotypes 1, 9 or 11 were not significantly different. The positive ELISA reaction with anti-serotypes 9 and 11 was unexpected with the CPS, which are supposed to be serotype-specific; LPS, and to a lesser extent proteins, were present in the CPS and appeared to be responsible for this reaction. In addition, sera from animals exposed to a field strain of A. pleuropneumoniae serotype 3 and to Actinobacillus suis presented a significantly lower mean OD (P < 0.001) when LC-LPS were used. Cross-reacting antigens consisted mainly of LPS core-lipid A present in the SBE and CPS. The specificity and the sensitivity of the ELISA were evaluated using three different cut-off values (the OD plus two, three and four times the standard deviation or SD) obtained with 667 negative sera. The diagnostic sensitivity was of 81% with the three antigens and the different thresholds. The diagnostic specificity was of 84, 86 and 88% for the mean plus two, three and four times the SD respectively using the SBE and the CPS, while that obtained with the LC-LPS was of 96, 98 and 99% using the same thresholds. In conclusion, LC-LPS make an easily obtainable antigen and seem to retain the best specificity while minimizing losses of sensitivity.