Mechanistic modelling for African swine fever transmission in the Republic of Korea.

Under the current African swine fever (ASF) epidemic situation, a science-based ASF-control strategy is required. An ASF transmission mechanistic model can be used to understand the disease transmission dynamics among susceptible epidemiological units and evaluate the effectiveness of an ASF-control strategy by simulating disease spread results with different control options. The force of infection, which is the probability that a susceptible epidemiological unit becomes infected, could be estimated by applying an ASF transmission mechanistic model. The government needs to plan an ASF-control strategy based on an ASF transmission mechanistic model.

Spatial epidemiology of highly pathogenic avian influenza subtype H5N6 in Gyeonggi Province, South Korea, 2016-2017.

Over 4 months in the winter of 2016-2017, 343 poultry farms in South Korea reported highly pathogenic avian influenza (HPAI) H5N6 occurrences, leading to the culling of 40 million poultry. Our study aimed to describe the spatial epidemiology of the 2016-2017 HPAI H5N6 outbreak in Gyeonggi Province, the most affected area in South Korea, comprising 35.9% (123) of the HPAI-infected poultry farms, to identify spatial risk factors for the increased probability of HPAI H5N6 occurrence, and to delineate areas with the highest likelihood of infection among different target poultry species. Although the poultry density was risk factor for the all species, rice paddy was only identified as risk factor for chicken and duck farms, not for other species farms suggesting that different biosecurity measures are required depending on the species. Although spatial effects of HPAI occurrence tended to be clustered within 16 km, the cluster range was reduced to 7 km when considering the identified risk factors, indicating a more geographically focused outbreak response when taking risk factors into account. The areas identified with the highest likelihood of infection can provide evidence, with accessibility to policymakers, to improve risk-based surveillance for HPAI. Our findings provide epidemiological understanding helpful in improving surveillance activity and assisting in the design of more cost-effective intervention policies related to future HPAI outbreaks in South Korea.

Understanding the transmission of African swine fever in wild boars of South Korea: A simulation study for parameter estimation.

Since the introduction of African swine fever (ASF) to Georgia in 2007, the disease has spread to many other countries including South Korea. Initial detection of ASF from wild boars (WB) in South Korea was reported in early October 2019. Since then, more than a thousand WB samples collected from the northern part of the country have been confirmed as ASF positive (2.9% of ASF positivity among WB samples collected until June 2020), indicating that the disease is endemic in the WB populations. To control the disease, multiple layers of fence-lines have been erected. Nevertheless, outbreaks continuously occurred across the fence, requiring a better understanding of the spatial transmission mechanism of ASF in WBs. Hence, we developed a novel ASF transmission model to estimate ecological and epidemiological parameters related to the spread of the disease in the WB population of South Korea. The results showed that roads and rivers were effective to prevent the spread, reducing the transmission rate to approximately 37% on average. Only a limited level of reduction was indicated via fence-lines, implying erection of fences might be considered as a temporary measure to delay the spread. This study also revealed that the probability of ASF transmission to adjacent habitats considerably decreased with increasing distance, supporting the slow spatial transmission speed reported from other European countries. Considering that elucidation of ASF dynamics in WB is crucial to mitigate the impact of the disease, we believe this study provides some useful ecological and epidemiological implications to control the disease in future.

Basic reproduction number of African swine fever in wild boars (Sus scrofa) and its spatiotemporal heterogeneity in South Korea.

BACKGROUND: African swine fever (ASF) is a hemorrhagic fever occurring in wild boars (Sus scrofa) and domestic pigs. The epidemic situation of ASF in South Korean wild boars has increased the risk of ASF in domestic pig farms. Although basic reproduction number (R0) can be applied for control policies, it is challenging to estimate the R0 for ASF in wild boars due to surveillance bias, lack of wild boar population data, and the effect of ASF-positive wild boar carcass on disease dynamics. OBJECTIVES: This study was undertaken to estimate the R0 of ASF in wild boars in South Korea, and subsequently analyze the spatiotemporal heterogeneity. METHODS: We detected the local transmission clusters using the spatiotemporal clustering algorithm, which was modified to incorporate the effect of ASF-positive wild boar carcass. With the assumption of exponential growth, R0 was estimated for each cluster. The temporal change of the estimates and its association with the habitat suitability of wild boar were analyzed. RESULTS: Totally, 22 local transmission clusters were detected, showing seasonal patterns occurring in winter and spring. Mean value of R0 of each cluster was 1.54. The estimates showed a temporal increasing trend and positive association with habitat suitability of wild boar. CONCLUSIONS: The disease dynamics among wild boars seems to have worsened over time. Thus, in areas with a high elevation and suitable for wild boars, practical methods need to be contrived to ratify the control policies for wild boars.

Modelling the Spatial Distribution of ASF-Positive Wild Boar Carcasses in South Korea Using 2019-2020 National Surveillance Data.

In September 2019, African swine fever (ASF) was reported in South Korea for the first time. Since then, more than 651 ASF cases in wild boars and 14 farm outbreaks have been notified in the country. Despite the efforts to eradicate ASF among wild boar populations, the number of reported ASF-positive wild boar carcasses have increased recently. The purpose of this study was to characterize the spatial distribution of ASF-positive wild boar carcasses to identify the risk factors associated with the presence and number of ASF-positive wild boar carcasses in the affected areas. Because surveillance efforts have substantially increased in early 2020, we divided the study into two periods (2 October 2019 to 19 January 2020, and 19 January to 28 April 2020) based on the number of reported cases and aggregated the number of reported ASF-positive carcasses into a regular grid of hexagons of 3-km diameter. To account for imperfect detection of positive carcasses, we adjusted spatial zero-inflated Poisson regression models to the number of ASF-positive wild boar carcasses per hexagon. During the first study period, proximity to North Korea was identified as the major risk factor for the presence of African swine fever virus. In addition, there were more positive carcasses reported in affected hexagons with high habitat suitability for wild boars, low heat load index (HLI), and high human density. During the second study period, proximity to an ASF-positive carcass reported during the first period was the only significant risk factor for the presence of ASF-positive carcasses. Additionally, low HLI and elevation were associated with an increased number of ASF-positive carcasses reported in the affected hexagons. Although the proportion of ASF-affected hexagons increased from 0.06 (95% credible interval (CrI): 0.05-0.07) to 0.09 (95% CrI: 0.08-0.10), the probability of reporting at least one positive carcass in ASF-affected hexagons increased from 0.49 (95% CrI: 0.41-0.57) to 0.73 (95% CrI: 0.66-0.81) between the two study periods. These results can be used to further advance risk-based surveillance strategies in the Republic of Korea.

Interpretation of the Basic and Effective Reproduction Number.

In epidemiology, the basic reproduction number (R0) is a term that describes the expected number of infections generated by 1 case in a susceptible population. At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, R0 was frequently referenced by the public health community and the wider public. However, this metric is often misused or misinterpreted. Moreover, the complexity of the process of estimating R0 has caused difficulties for a substantial number of researchers. In this article, in order to increase the accessibility of this concept, we address several misconceptions related to the threshold characteristics of R0 and the effective reproduction number (Rt). Moreover, the appropriate interpretation of the metrics is discussed. R0 should be considered as a population-averaged value that pools the contact structure according to a stochastic transmission process. Furthermore, it is necessary to understand the unavoidable time lag for Rt due to the incubation period of the disease.

KMRC011, an agonist of toll-like receptor 5, mitigates irradiation-induced tissue damage and mortality in cynomolgus monkeys.

In the study here, the potential applicability of KMRC011 - an agonist of toll-like receptor-5 - as a countermeasure for radiation toxicities was evaluated. Following a single 5.5 Gy total body irradiation (TBI, surface absorbed dose = 7 Gy) of Co60 γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received TBI only and a group that was injected once with KMRC011 (10 µg/kg) after TBI. Compared to the TBI-only hosts (80%), the death rate was significantly improved by the use of KMRC011 (40%), all deaths in both groups occurred in the period from Days 19-24 post-TBI. Further analysis of monkeys that survived until the end of the experiment showed that AST and ALT levels were elevated only in the TBI group, and that radiation-induced tissue damage was alleviated by the KMRC011 injection. Additionally, expression of cell death-related proteins was lower in tissues from the KMRC011-treated hosts than in those in the TBI-only group. Other measured parameters, including body weight, food uptake, and hematological values did not significantly differ between the two groups over the entire period. The results of this study, thus demonstrate that KMRC011 could potentially be used as a medical countermeasure for the treatment of acute radiation exposure.

Repeated injection of KMRC011, a medical countermeasure for radiation, can cause adverse health effects in cynomolgus monkeys.

High-dose radiation-induced tissue damage is a major limiting factor in the medical application of nuclear technology. Herein, we tested 28-day repeated-dose toxicity of KMRC011, an agonist of toll-like receptor (TLR) 5, which is being developed as a medical countermeasure for radiation, using cynomolgus monkeys. KMRC011 (0.01, 0.02 or 0.04 mg/kg/day) was intramuscularly injected once daily for 4 weeks, and each two monkeys in both control and 0.04 mg/kg/day group were observed for an additional 2-week recovery period. There were no dose-related toxicological changes in mortality, clinical observations, body weight, food consumption, ophthalmological findings, electrocardiographs, coagulation, serum chemistry, organ weights, or urinalysis and urine chemistry. Although treatment-related changes, such as increased white blood cells, increased absolute and relative neutrophils, decreased relative lymphocytes and inflammatory lesions, were noted in the maximum dose group, these findings were not observed after the 2-week recovery period. Further, we considered that the kidneys and heart may be target organs of TLR5 agonists, as well as the spleen, and that autophagic signals can be triggered in tissue damage and the repair process. Importantly, accumulation of p62 protein, an indicator of autophagy, and a decrease of caveolin-1 protein, a regulator of TLR5 protein half-life, were found in both tissues from the highest dose group. Therefore, we conclude that the no-observed-adverse-effect level for KMRC011 may be greater than 0.04 mg/kg/day in male and female monkeys. Additionally, we propose that further studies are needed to identify the molecular signals, which are related to KMRC011-induced adverse effects.

Evaluation of changes in cardiac biomarker concentrations and enzyme activities in serum after short- and long-duration transcutaneous cardiac pacing in dogs.

OBJECTIVE: To evaluate serum cardiac biomarker concentrations and selected enzyme activities in dogs with experimentally induced bradyarrhythmias after short- (1-hour) and long- (3-hour) duration transcutaneous cardiac pacing (TCP). ANIMALS: 10 healthy Beagles. PROCEDURES: In each dog, anesthesia was induced with propofol (5 mg/kg, IV) and maintained via inhalation of isoflurane in oxygen. To induce bradyarrhythmia, diltiazem was administered IV (20 to 50 mg/dog). Transcutaneous cardiac pacing was performed for 1 hour (5 dogs) or 3 hours (5 dogs) by use of an automated external cardiac pulse generator and a transdermal electrode. Serum concentrations of creatine kinase-MB fraction and cardiac troponin I and activities of aspartate transaminase, creatine kinase, and lactate dehydrogenase were evaluated the day before (baseline) and at intervals until 7 days after TCP. RESULTS: Increases (from baseline) in serum cardiac biomarker concentrations and enzyme activities were detected in the long-duration TCP group; changes in the short-duration TCP group were more minor and largely not significant. Although severity of myocardial and skeletal muscular injuries was apparently greater with greater duration of TCP, the injuries were not persistent; most variables were within reference range within 3 days after TCP. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that application of TCP for > 1 hour in dogs may cause myocardial and skeletal muscular injuries. Serum concentrations of creatine kinase-MB fraction and cardiac troponin I and activities of aspartate transaminase, creatine kinase, and lactate dehydrogenase should be more carefully monitored after TCP of > 1 hour's duration to evaluate potential myocardial damages.

Effects of dietary iron levels on growth performance, hematological status, liver mineral concentration, fecal microflora, and diarrhea incidence in weanling pigs.

An experiment was conducted in weanling pigs (Landrace x Yorkshire x Duroc) to evaluate the effects of dietary iron levels on growth performance, hematological status, liver mineral concentration, fecal microflora, and diarrhea incidence. One hundred and forty-four piglets (initial BW 5.96 +/- 0.93 kg) were randomly allotted to one of the four dietary treatments on the basis of their body weights. The basal diets for each phase (phase 1: days 0 to 14; phase 2: days 15 to 28) were formulated to contain minimal Fe and then supplemented with gradient levels of Fe (0, 50, 100, and 250 mg/kg) from ferrous sulfate. Feces were collected on days 14 and 28 and used for the analysis of microbial count and trace minerals. Eight piglets from each treatment (two piglets per pen) were bled at 0, 7, 14, 21, and 28 days to determine their hematological and plasma Fe status. In addition, two piglets from each pen (eight piglets per treatment) were killed at days 14 and 28 to determine liver mineral concentrations. Pigs fed supplemental 250 ppm Fe showed lowest overall average daily gain (linear, p = 0.036). Diarrhea incidence was linearly increased (p < 0.001) with supplemental Fe level. On days 14, coliform population in normal feces was increased (p = 0.036) linearly with supplemental Fe level, and there were higher (p = 0.043) coliform population and lower (p < 0.001) Bifidobacterium spp. in the diarrhea feces. Supplemental Fe linearly (p < 0.05) improved the total red blood cells, hemoglobin, plasma, and liver (p = 0.109) Fe status of pigs and also increased (linear and quadratic, p < 0.001) the fecal excretion of Fe on days 14 and 28. It is concluded that increasing the dietary iron levels in piglets improved their hematological status and liver Fe content; however, higher dietary Fe levels might also be associated with the increased diarrhea incidence.

Enhanced expressions of arginine vasopressin (Avp) in the hypothalamic paraventricular and supraoptic nuclei of type 2 diabetic rats.

Arginine vasopressin (AVP) is known to a neuropeptide that plays important roles in water conservation, sodium homeostasis, and in the regulation of serum osmolality. Several studies have reported that the elevated AVP level is related with diabetes mellitus as an acute or chronic stressor using type 1 diabetes mellitus animal models. However, it is unclear as to how the immunoreactivity and protein level of AVP in the brain is regulated in animal models of type 2 diabetes mellitus. In the present study, Zucker diabetic fatty (ZDF) rats were employed as a type 2 diabetes mellitus model and were compared with Zucker lean control (ZLC) rats with respect to AVP protein expression. Furthermore, in order to verify the regulation of AVP expression before and after the onset of diabetes mellitus, pre-diabetic rats (4 week-old) and obese-diabetic rats (12 week-old) were used. Blood glucose levels and water consumption were also measured and the results showed significantly high in 12 week-old ZDF than any other groups. AVP expression levels in the paraventricular nucleus and supraoptic nucleus were found to be significantly higher in 12 week-old ZDF rats than in 12 week-old ZLC rats and than in 4 week-old rats by immunostaining and western blotting. Enhanced expression of AVP in these animals may be associated with type 2 diabetes mellitus.

Comparison of tissue and fluid samples for the early detection of canine distemper virus in experimentally infected dogs.

The clinical utility of various specimens was examined for the early diagnosis of canine distemper (CD). Seven healthy dogs at 17 weeks of age were experimentally infected with a field isolate of canine distemper virus. The RT-PCR was carried out to detect CDV NP gene. Dogs showed mild fever and leukopenia, however, typical clinical signs of CD were not seen through the experimental period. CDV amplicons were detected more, earlier and for longer period in the conjunctival swabs than in the other samples employed. These results suggested that conjunctival swab samples, which are easy to obtain and non-invasive, would be the most suitable and practical specimen for the early antemortem diagnosis of CDV infection.

Variations in the nucleocapsid protein gene of infectious bronchitis viruses isolated in Korea.

Fourteen infectious bronchitis viruses (IBVs) were isolated in Korea between 2001 and 2003 from chickens suspected to be infected with IBVs. The nucleocapsid (N) protein genes of the various IBVs were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and were cloned and sequenced, and the nucleotide and deduced amino acid sequences were compared with published sequences for non-Korean IBV strains. The Korean IBV isolates shared amino acid sequence similarity of between 89.2% (K203-02 and K1255-03) and 98.3% (K434-01 and K281-01) with each other and exhibited amino acid sequence similarity between 57.0% (K774-01 and V18/91) and 96.6% (K507-01 and JP8147) with non-Korean IBV strains. Phylogenetic analysis of the deduced N protein amino acid sequences resulted in the segregation of Korean IBV isolates into three different clusters, with cluster assignments differing for some of the isolates from those obtained with analysis of the S1 glycoprotein. Korean IBV isolates K069-01, K281-01, K434-01, K504-01, K774-01, K748-01, K044-02, K058-02, K161-02, K203-02, and K234-02 formed an independent cluster comprised only of Korean IBV isolates. Another Korean IBV isolate, K210-02, belonged to a cluster that included IBV strains isolated in USA, the Netherlands and China. Recent Korean IBV isolates K514-03 and K1255-03 grouped into a third distinct cluster related to a Chinese IBV strain. As deduced from phylogenetic analysis, some IBV isolates appear to have arisen from the recombination of IBV strains with different origins.

Estimation of paratuberculosis prevalence in dairy cattle in a province of Korea using an enzyme-linked immunosorbent assay: application of Bayesian approach.

To draw inferences about the sensitivity and specificity of the newly developed ELISA test for bovine paratuberculosis (PTB) diagnosis and posterior distribution on the prevalence of PTB in a province of Korea, we applied Bayesian approach with Gibbs sampler to the data extracted from the prevalence study in 1999. The data were from a single test results without a designated gold test. The prevalence estimates for PTB in study population ranged 3.2-5.3% for conservative and 6.7-7.1% for liberal, depending on the priors used. The simulated specificities of the ELISA close to one another, ranging 84.7-90.6%, whereas the sensitivity was somewhat spread out depending largely on the priors with a range of 46.4-88.2%. Our findings indicate that the ELISA method appeared useful as a screening tool at a minimum level in comparison to other diagnostic tests available for this disease in terms of sensitivity. However, this advantage comes at a cost of having low specificity of the test.

Prevalence and risk factors for contamination with Listeria monocytogenes of imported and exported meat and fish products in Switzerland, 1992-2000.

A total of 2053 import and 164 export samples from 425 production plants were examined over a 9-year period (1992-2000) for the presence of Listeria monocytogenes (L. monocytogenes) in Switzerland. Overall, 282 samples (12.2%) and 85 plants (20.5%) harbored the pathogen. The highest isolation risk was for marinated fish (38%); the lowest was in cured- and dried-meat products. Unconditional fixed-effect logistic regression was used to identify the main hazards associated with the presence of L. monocytogenes. The plant-level model considered potential risk factors for a positive culture operating at the production-plant level by including a random effect of plant and year. Food category was the only significant factor; sampling site, country of origin and season were not significant. Marinated fish was a strong predictor for positive culture, whereas cooked- and cured-meat products were protective. Plant and year effects were significant. Control measures should be focused on specific food items in each production plant.

Risk factors for L. monocytogenes contamination of dairy products in Switzerland, 1990-1999.

Our purpose was to identify the main hazards associated with the spread of Listeria monocytogenes in dairy products in Switzerland and to determine the changes in predominant serotypes of the isolates, using databases on dairy-processing and environments from the Swiss Dairy Research Station during the years 1990-1999. Overall, of 76,271 samples collected, 3722 (4.9%) were positive for the presence of L. monocytogenes. Cheese-ripening facilities had the highest proportion of positive samples (7.6%), followed by small-scale local dairies (4.4%). By sample type, the highest proportion of positive samples (9.5%) was observed in water samples used for cheese-washing, followed by cheese-surface swabs (5.0%). During the 10-year period, no positive samples were obtained from cream, ice cream, milk powder, yogurt, or fresh cheese. Of 3722 L. monocytogenes isolates, 1328 (35.7%) were serologically typeable. Serotypes 1/2a, 1/2b, and 4b accounted for 92.7% of the 1328 isolates. Until 1995, the most-prevalent serotype was 1/2b (annual proportional prevalence 39.3-72.2%)--whereas since 1996, 1/2a was the most prevalent (34.7-54.7%). During 1996-1999, serotype 1/2a increased by 88%, compared to the average of 1990-1995. In the final random-effect multivariable logistic model, the strongest predictor of a positive culture was samples from cheese-ripening plant (OR=1.54; 95% CI: 1.14, 2.08) and the second-strongest predictor was samples collected by someone who was employed by the plant (OR=1.48; 1.29, 1.71). Hard and semi-hard cheeses were more likely to be associated with serotype 1/2b and soft cheeses with serotype 1/2a.