Modelling the Innate Immune Response against Avian Influenza Virus in Chicken.

At present there is limited understanding of the host immune response to (low pathogenic) avian influenza virus infections in poultry. Here we develop a mathematical model for the innate immune response to avian influenza virus in chicken lung, describing the dynamics of viral load, interferon-α, -ß and -γ, lung (i.e. pulmonary) cells and Natural Killer cells. We use recent results from experimentally infected chickens to validate some of the model predictions. The model includes an initial exponential increase of the viral load, which we show to be consistent with experimental data. Using this exponential growth model we show that the duration until a given viral load is reached in experiments with different inoculation doses is consistent with a model assuming a linear relationship between initial viral load and inoculation dose. Subsequent to the exponential-growth phase, the model results show a decline in viral load caused by both target-cell limitation as well as the innate immune response. The model results suggest that the temporal viral load pattern in the lungs displayed in experimental data cannot be explained by target-cell limitation alone. For biologically plausible parameter values the model is able to qualitatively match to data on viral load in chicken lungs up until approximately 4 days post infection. Comparison of model predictions with data on CD107-mediated degranulation of Natural Killer cells yields some discrepancy also for earlier days post infection.

Airborne transmission of a highly pathogenic avian influenza virus strain H5N1 between groups of chickens quantified in an experimental setting.

Highly pathogenic avian influenza (HPAI) is a devastating viral disease of poultry and quick control of outbreaks is vital. Airborne transmission has often been suggested as a route of transmission between flocks, but knowledge of the rate of transmission via this route is sparse. In the current study, we quantified the rate of airborne transmission of an HPAI H5N1 virus strain between chickens under experimental conditions. In addition, we quantified viral load in air and dust samples. Sixteen trials were done, comprising a total of 160 chickens housed in cages, with three treatment groups. The first group was inoculated with strain A/turkey/Turkey/1/2005 H5N1, the second and third group were not inoculated, but housed at 0.2 and 1.1m distance of the first group, respectively. Tracheal and cloacal swabs were collected daily of each chicken to monitor virus transmission. Air and dust samples were taken daily to quantify virus load in the immediate surroundings of the birds. Samples were tested by quantitative RRT-PCR and virus isolation. In 4 out of 16 trials virus was transmitted from the experimentally inoculated chickens to the non-inoculated chickens. The transmission rate was 0.13 and 0.10 new infections per infectious bird at 0.2m and 1.1m, respectively. The difference between these estimates was, however, not significant. Two air samples tested positive in virus isolation, but none of these samples originated from the trials with successful transmission. Five dust samples were confirmed positive in virus isolation. The results of this study demonstrate that the rate of airborne transmission between chickens over short distances is low, suggesting that airborne transmission over a long distance is an unlikely route of spread. Whether or not this also applies to the field situation needs to be examined.

The effect of inoculation dose of a highly pathogenic avian influenza virus strain H5N1 on the infectiousness of chickens.

Highly pathogenic avian influenza is of major concern for the poultry industry, as the virus can spread rapidly in and between flocks, causing high mortality and severe economic losses. The aim of this study was to determine the probability of infection and to determine dose-dependent virus transmission (direct transmission) for various inoculation doses. Two transmission experiments with pair-wise housed layer type chickens were performed, in which one bird per pair was inoculated with an HPAI H5N1 virus and the other contact-exposed. Various inoculation doses were used to determine the susceptibility (ID(50)), and possible relation between ID(50), and infectiousness, expressed as the amount of virus shedding and the probability of contact birds becoming infected. The infectious H5N1 dose (CID(50)) in this study was an estimated 10(2.5) egg infectious dose (EID(50))(.) Increasing the dose increased the probability of infection but survival from infection was independent of dose. In addition, increasing the dose decreased the mean latent period in the inoculated chickens significantly. This could be important for determining the time of onset of infection in a flock and thus allowing more accurate identification of the source of infection. Moreover, the amount of virus shed in trachea and cloaca by the inoculated chickens in the time between inoculation and contact infection, also differed between the various dose groups. Despite differences in latent period and virus shedding, the transmission rate parameter ß and reproduction ratio R(0) did not differ significantly between the various dose groups. This implies that in this experiment the amount of virus shedding is not a measure to predict transmission or the infectiousness of chickens.