Evaluating the utility of national-scale data to estimate the local risk of foot-and-mouth disease in endemic regions.

Knowledge of the distribution of foot-and-mouth disease (FMD) is required if control programmes are to be successful. However, data on the seroprevalence and incidence of affected villages in developing countries with endemic disease are scarce. This is partly due to resource constraints as well as the logistical challenges of conducting intensive surveys and diagnostic testing in remote locations. In this study, we evaluated the performance of low resolution national-scale data against high resolution local survey data to predict the FMD serological status of 168 villages in the Mandalay and Sagaing Regions of central Myanmar using both logistic regression and random forest modelling approaches. Blood samples for ELISA testing were collected from approximately 30 cattle per village in both the 6 to 18 month age range and in the over 18 month age range to distinguish between recent and historical exposure, respectively. The results of the animal level tests were aggregated to the village level to provide the outcome of interest (village positive or not positive for FMD), and three explanatory data sets were constructed: using only nationally available data, using only data collected by survey and using the combined survey and nationally available data. The true seroprevalence of FMD at the village level was 61% when only young animals were included, but increased to 87% when all animals were included. The best performing model was a logistic regression model using the combined national and survey data to predict recent infection in villages. However, this still incorrectly classified 40% of villages, which suggests that using national-level data were not reliable enough for extrapolating seroprevalence in regions where conducting detailed surveys is impractical. Other methods for collected data on FMD such as the use of local reporting should be explored.

Estimating foot-and-mouth disease (FMD) prevalence in central Myanmar: Comparison of village headman and farmer disease reports with serological findings.

The impacts of foot-and-mouth disease (FMD) on food security in developing countries are difficult to quantify due to the scarcity of accurate data on the prevalence and incidence of affected villages. This is partly due to resource constraints as well as the logistical challenges of conducting regular diagnostic testing in remote locations. In this study, we used descriptive analysis and latent class analysis (LCA) models to analyse data collected during a field survey of 160 villages in central Myanmar in the Mandalay and Sagaing Regions over the 2012-2016 time period. We evaluated the performance of verbal reports made by village householders and headmen against serological data to retrospectively determine the FMD-infection status of our study area and to identify factors contributing to under-reporting. Blood samples were collected from approximately 30 cattle per village in both the 6- to 18-month age range and over 18-month age range to distinguish between recent and historic exposure. Village householders were asked to identify pictures of FMD-affected cattle amongst pictures of cattle affected with other common endemic diseases to assess the accuracy of their verbal reporting. The serological results confirmed that FMD is endemic in central Myanmar with village-level seroprevalence estimated at 56% for animals 6-18 months of age and 80% when all age groups were considered together. Most village householders were familiar with the clinical signs of FMD-affected cattle (72%). Based on the results from the LCA models, the village headman had a sensitivity of 77% and specificity of 75% for identifying FMD outbreaks in their village, whereas individual householders had a higher sensitivity and lower specificity of 80% and 56%, respectively. The level of disagreement between the different sources was correlated with the total number of cattle in the village and may potentially be worse in villages where endemic FMD may have led to a high level of natural immunity in cattle and subsequent masking of clinical signs. However, other regional effects such as the intensity of FMD extension efforts cannot be ruled out. Overall, the results suggest that verbal reports of FMD outbreaks from village headmen may be a useful tool to integrate into active FMD surveillance programmes in developing countries.

Ubiquitin-regulated recruitment of IkappaB kinase epsilon to the MAVS interferon signaling adapter.

Induction of the antiviral interferon response is initiated upon recognition of viral RNA structures by the RIG-I or Mda-5 DEX(D/H) helicases. A complex signaling cascade then converges at the mitochondrial adapter MAVS, culminating in the activation of the IRF and NF-kappaB transcription factors and the induction of interferon gene expression. We have previously shown that MAVS recruits IkappaB kinase epsilon (IKKepsilon) but not TBK-1 to the mitochondria following viral infection. Here we map the interaction of MAVS and IKKepsilon to the C-terminal region of MAVS and demonstrate that this interaction is ubiquitin dependent. MAVS is ubiquitinated following Sendai virus infection, and K63-linked ubiquitination of lysine 500 (K500) of MAVS mediates recruitment of IKKepsilon to the mitochondria. Real-time PCR analysis reveals that a K500R mutant of MAVS increases the mRNA level of several interferon-stimulated genes and correlates with increased NF-kappaB activation. Thus, recruitment of IKKepsilon to the mitochondria upon MAVS K500 ubiquitination plays a modulatory role in the cascade leading to NF-kappaB activation and expression of inflammatory and antiviral genes. These results provide further support for the differential role of IKKepsilon and TBK-1 in the RIG-I/Mda5 pathway.