14th ICID - Poster Abstracts - International Society for Infectious ...

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When citing these abstracts please use the following reference: Author(s) of abstract. Title of abstract [abstract]. Int J Infect Dis 2010;14S1: Abstract number. Please note that the official publication of the International Journal of Infectious Diseases 2010, Volume 14, Supplement 1 is available electronically on http://www.sciencedirect.com Final Abstract Number: 73.008 Session: Animal Models, Pathogenesis & Host Defenses Date: Friday, March 12, 2010 Time: 12:30-13:30 Room: Poster & Exhibition Area/Ground Level Type: Poster Presentation Natural history study of a low dose HPAI (A/Vietnam/1203/04) infection in ferrets J. Long 1 , J. Edwards 1 , A. Wasko 1 , M. Gainey 1 , P. Herr-Calomeni 1 , G. Stark 2 , J. Bigger 2 1 Battelle , Columbus, OH, USA, 2 Battelle, Columbus, OH, USA Background: The objective of this study was to refine a low dose ferret therapeutic model of A/Vietnam/1203/04 influenza infection. Methods: Forty-four male ferrets (Mustela putorius furo), 8-15 weeks in age, were divided into 4 groups of 8 ferrets (groups A, C, E and G; experimental) and 4 groups of 3 ferrets (groups B, D, F and H; controls). Animals in groups A, C, E and G were challenged with 5 x 103 TCID50 of A/Vietnam/1203/04 via the intranasal route. Data collection was staggered by group pairs (groups A+B, C+D, E+F, G+H) so that clinical observations, blood (clinical hematology and clinical chemistry), nasal wash specimens (qPCR and TCID50), and temperature data were collected at approximately 8 hour intervals from 16-48 hours and at 24 hour intervals between 72 and 120 hours. After 120 hours, temperatures and clinical observations were recorded 2 times daily until the end of the study (Day 14) or death of the animal. Tissues were collected from any infected animal found dead or euthanized prior to day 14, for determination of viral load by a combination of qPCR and TCID50. Results: All animals challenged with A/Vietnam/1203/04 succumbed. Observations for infected animals included: 1) significant decreases in body weight on all study days, 2) significant increases in body temperature as early as 1 day post-challenge, and 3) significant changes in clinical activity beginning at 40 hours. Analysis of clinical hematology data for peripheral blood specimens revealed significant differences between control and infected animals as early as 32 – 48 hours post-challenge for lymphocytes, white blood cells, and platelets. Significant persistent clinical chemistry parameter changes were limited to serum glucose, albumin, calcium and phosphorous. Results of TCID50 assays and qPCR demonstrated virus shedding in nasal wash specimens as well as high viral titers in a number of tissues (brain, olfactory bulb, liver, lung, and nasal turbinates). Conclusion: This study identified a combination of clinical parameters that can be used to characterize early onset of disease following a low dose A/Vietnam/1203/04 challenge.
When citing these abstracts please use the following reference: Author(s) of abstract. Title of abstract [abstract]. Int J Infect Dis 2010;14S1: Abstract number. Please note that the official publication of the International Journal of Infectious Diseases 2010, Volume 14, Supplement 1 is available electronically on http://www.sciencedirect.com Final Abstract Number: 73.009 Session: Animal Models, Pathogenesis & Host Defenses Date: Friday, March 12, 2010 Time: 12:30-13:30 Room: Poster & Exhibition Area/Ground Level Type: Poster Presentation FcR IIA polymorphism -131H/R and malaria severity in Ghanaian children D. Amoako-Sakyi University of Cape Coast, Cape Coast, C/R, Ghana Background: Plasmodium falciparum malaria still remains a major public health problem in most parts of the world especially in Sub Saharan Africa. Pathogenesis of severe malaria is still not fully understood and several factors have been suggested to play a role. Fc receptors constitutes a crucial link between humoral and cellular immune responses and are thought be important in the pathogenesis of severe malaria. FcRIIA which belongs to the family of Fc receptors are predominantly expressed on neutrophils which have been shown to kill merozoites. Thus variants of FcRIIA may influence the binding affinity of IgG and subsequently affect phagocytosis and parasite clearance. On the other hand, increased binding affinity and enhanced phagocytosis can also stimulate the release of some immune factors in quantities that are detrimental leading to severe malaria. The objective of this study was to investigate the role of the FcRIIA-131H/R variant in the pathogenesis of severe malaria in Ghanaian children. Methods: This study was a hospital based unmatched case-control study involving 290 malaria cases and controls. The study was conducted at the Korle-Bu Teaching Hospital in Accra, Ghana. PCR-RFLP was used to characterize the FcRIIA-131H/R polymorphism in 210 Ghanaian children with uncomplicated malaria, severe malaria anaemia, and cerebral malaria. Results: The study revealed that the 131HH genotype is associated with susceptibility to cerebral malaria (OR = 4.0, 95% CI = 1.28 – 12.52; p = 0.014). The results also revealed that carriers of the R allele had a significantly lower parasitaemia (p < 0.050) than non-carriers. Conclusion: The presence of FcRIIA-131HH which is regarded as a low affinity variant may lead to decreased phagocytosis and poor control of parasitaemia in Ghanaian Children. This however does not exclude the possibility that IgG binding to the FcRIIA-131HH variant can stimulate the release of factors that may contribute to the development cerebral malaria.
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