Sasidhar Malladi

An Outcomes Model to Evaluate Risks and Benefits of Escherichia coli Vaccination in Beef Cattle

We developed a stochastic simulation model to evaluate the impact of Escherichia coli O157:H7 (O157) vaccination on key epidemiological outcomes. The model evaluated a reduction in the O157 prevalence in feedlot cattle as well as concentration in cattle feces due to vaccination. The impact of this reduction on outcomes at slaughter/harvest and consumption was evaluated by simulating the relationships between the O157 prevalence and concentration at various points in the ground beef supply chain. The uncertainty and variability associated with the O157 contamination was explicitly modeled in production, slaughter, and consumption modules. Our results show that vaccination can have a significant benefit with respect to relevant outcomes such as (1) the number of human O157 illnesses due to the consumption of ground beef, (2) the number of production lots with high O157 contamination levels, (3) the likelihood of detection by U.S. Department of Agriculture Food Safety and Inspection Service testing, and (4) the probability of multiple illnesses due to ground beef servings from the same lot. These results show that these outcomes are strongly impacted by preharvest vaccination. For example, if the vaccine is used so as to reduce the prevalence of E. coli shedding cattle by 80% and if all U.S. steers and heifers were vaccinated, the expected number of human illnesses from ground beef-associated O157 would be reduced almost 60%. If the vaccine is 60% or 40% effective, the illness rate would be reduced approximately 45% or 40%, respectively. The number of production lots (10,000-lb lots) with high O157 contamination levels (> 1000 servings) would be reduced by 96% if all steers and heifers received an 80% effective vaccine regimen. The analysis shows that resulting reduction in the number of shedding animals and the reduced concentration of E. coli on carcasses can combine to reduce human illnesses and cost to beef packers.

A Stochastic Assessment of the Public Health Risks of the Use of Macrolide Antibiotics in Food Animals

Campylobacteriosis is an important food-borne illness with more than a million U.S. cases annually. Antibiotic treatment is usually not required. However, erythromycin, a macrolide antibiotic, is recommended for the treatment of severe cases. Therefore, it is considered a critically important antibiotic and given special attention as to the risk that food animal use will lead to resistant infections and compromised human treatment. To assess this risk, we used a retrospective approach; estimating the number of campylobacteriosis cases caused by specific meat consumption utilizing the preventable fraction. We then determined the number of cases with macrolide resistance Campylobacter spp. based on a linear model relating the resistance fraction to on-farm macrolide use. In this article, we considered the uncertainties in the parameter estimates, utilized a more elaborate model of resistance development and separated C. coli and C. jejuni. There are no published data for the probability of compromised treatment outcome due to macrolide resistance. Therefore, our estimates of compromised treatment outcome were based on data for fluoroquinolone-resistant infections. The conservative results show the human health risks are extremely low. For example, the predicted risk of suboptimal human treatment of infection with C. coli from swine is only 1 in 82 million; with a 95% chance it could be as high as 1 in 49 million. Risks from C. jejuni in poultry or beef are even less. Reduced antibiotic use can adversely impact animal health. These low human risks should be weighed against the alternative risks.

Impact of Virus Strain Characteristics on Early Detection of Highly Pathogenic Avian Influenza Infection in Commercial Table-Egg Layer Flocks and Implications for Outbreak Control

SUMMARY. Early detection of highly pathogenic avian influenza (HPAI) infection in commercial poultry flocks is a critical component of outbreak control. Reducing the time to detect HPAI infection can reduce the risk of disease transmission to other flocks. The timeliness of different types of detection triggers could be dependent on clinical signs that are first observed in a flock, signs that might vary due to HPAI virus strain characteristics. We developed a stochastic disease transmission model to evaluate how transmission characteristics of various HPAI strains might effect the relative importance of increased mortality, drop in egg production, or daily real-time reverse transcriptase (RRT)-PCR testing, toward detecting HPAI infection in a commercial table-egg layer flock. On average, daily RRT-PCR testing resulted in the shortest time to detection (from 3.5 to 6.1 days) depending on the HPAI virus strain and was less variable over a range of transmission parameters compared with other triggers evaluated. Our results indicate that a trigger to detect a drop in egg production would be useful for HPAI virus strains with long infectious periods (6–8 days) and including an egg-drop detection trigger in emergency response plans would lead to earlier and consistent reporting in some cases. We discuss implications for outbreak control and risk of HPAI spread attributed to different HPAI strain characteristics where an increase in mortality or a drop in egg production or both would be among the first clinical signs observed in an infected flock.

A Simulation-Based Evaluation of Premovement Active Surveillance Protocol Options for the Managed Movement of Turkeys to Slaughter During an Outbreak of Highly Pathogenic Avian Influenza in the United States

SUMMARY. Risk management decisions associated with live poultry movement during a highly pathogenic avian influenza (HPAI) outbreak should be carefully considered. Live turkey movements may pose a risk for disease spread. On the other hand, interruptions in scheduled movements can disrupt business continuity. The Secure Turkey Supply (STS) Plan was developed through an industry-government-academic collaboration to address business continuity concerns that might arise during a HPAI outbreak. STS stakeholders proposed outbreak response measure options that were evaluated through risk assessment. The developed approach relies on 1) diagnostic testing of two pooled samples of swabs taken from dead turkeys immediately before movement via the influenza A matrix gene real-time reverse transcriptase polymerase chain reaction (rRT-PCR) test; 2) enhanced biosecurity measures in combination with a premovement isolation period (PMIP), restricting movement onto the premises for a few days before movement to slaughter; and 3) incorporation of a distance factor from known infected flocks such that exposure via local area spread is unlikely. Daily exposure likelihood estimates from spatial kernels from past HPAI outbreaks were coupled with simulation models of disease spread and active surveillance to evaluate active surveillance protocol options that differ with respect to the number of swabs per pooled sample and the timing of the tests in relation to movement. Simulation model results indicate that active surveillance testing, in combination with strict biosecurity, substantially increased HPAI virus detection probability. When distance from a known infected flock was considered, the overall combined likelihood of moving an infected, undetected turkey flock to slaughter was predicted to be lower at 3 and 5 km. The analysis of different active surveillance protocol options is designed to incorporate flexibility into HPAI emergency response plans.

The Impact of Holding Time on the Likelihood of Moving Internally Contaminated Eggs from a Highly Pathogenic Avian Influenza Infected but Undetected Commercial Table-Egg Layer Flock

SUMMARY. Emergency response during a highly pathogenic avian influenza (HPAI) outbreak may involve quarantine and movement controls for poultry products such as eggs. However, such disease control measures may disrupt business continuity and impact food security, since egg production facilities often do not have sufficient capacity to store eggs for prolonged periods. We propose the incorporation of a holding time before egg movement in conjunction with targeted active surveillance as a novel approach to move eggs from flocks within a control area with a low likelihood of them being contaminated with HPAI virus. Holding time reduces the likelihood of HPAI-contaminated eggs being moved from a farm before HPAI infection is detected in the flock. We used a stochastic disease transmission model to estimate the HPAI disease prevalence, disease mortality, and fraction of internally contaminated eggs at various time points postinfection of a commercial table-egg layer flock. The transmission model results were then used in a simulation model of a targeted matrix gene real-time reverse transcriptase (RRT)-PCR testing based surveillance protocol to estimate the time to detection and the number of contaminated eggs moved under different holding times. Our simulation results indicate a significant reduction in the number of internally contaminated eggs moved from an HPAI-infected undetected flock with each additional day of holding time. Incorporation of a holding time and the use of targeted surveillance have been adopted by the U.S. Department of Agriculture in their Draft Secure Egg Supply Plan for movement of egg industry products during an HPAI outbreak.

Risk Reduction Modeling of High Pathogenicity Avian Influenza Virus Titers in Nonpasteurized Liquid Egg Obtained from Infected but Undetected Chicken Flocks

Control of highly pathogenic avian influenza (HPAI) outbreaks in poultry has traditionally involved the establishment of disease containment zones, where poultry products are only permitted to move from within a zone under permit. Nonpasteurized liquid egg (NPLE) is one such commodity for which movements may be permitted, considering inactivation of HPAI virus via pasteurization. Active surveillance testing at the flock level, using targeted matrix gene real-time reversed transcriptase-polymerase chain reaction testing (RRT-PCR) has been incorporated into HPAI emergency response plans as the primary on-farm diagnostic test procedure to detect HPAI in poultry and is considered to be a key risk mitigation measure. To inform decisions regarding the potential movement of NPLE to a pasteurization facility, average HPAI virus concentrations in NPLE produced from a HPAI virus infected, but undetected, commercial table-egg-layer flock were estimated for three HPAI virus strains using quantitative simulation models. Pasteurization under newly proposed international design standards (5 log10 reduction) is predicted to inactivate HPAI virus in NPLE to a very low concentration of less than 1 embryo infectious dose (EID)50 /mL, considering the predicted virus titers in NPLE from a table-egg flock under active surveillance. Dilution of HPAI virus from contaminated eggs in eggs from the same flock, and in a 40,000 lb tanker-truck load of NPLE containing eggs from disease-free flocks was also considered. Risk assessment can be useful in the evaluation of commodity-specific risk mitigation measures to facilitate safe trade in animal products from countries experiencing outbreaks of highly transmissible animal diseases.

Quantitative Estimation of the Number of Contaminated Hatching Eggs Released from an Infected, Undetected Turkey Breeder Hen Flock During a Highly Pathogenic Avian Influenza Outbreak

SUMMARY The regulatory response to an outbreak of highly pathogenic avian influenza (HPAI) in the United States may involve quarantine and stop movement orders that have the potential to disrupt continuity of operations in the U.S. turkey industry—particularly in the event that an uninfected breeder flock is located within an HPAI Control Area. A group of government-academic-industry leaders developed an approach to minimize the unintended consequences associated with outbreak response, which incorporates HPAI control measures to be implemented prior to moving hatching eggs off of the farm. Quantitative simulation models were used to evaluate the movement of potentially contaminated hatching eggs from a breeder henhouse located in an HPAI Control Area, given that active surveillance testing, elevated biosecurity, and a 2-day on-farm holding period were employed. The risk analysis included scenarios of HPAI viruses differing in characteristics as well as scenarios in which infection resulted from artificial insemination. The mean model-predicted number of internally contaminated hatching eggs released per movement from an HPAI-infected turkey breeder henhouse ranged from 0 to 0.008 under the four scenarios evaluated. The results indicate a 95% chance of no internally contaminated eggs being present per movement from an infected house before detection. Sensitivity analysis indicates that these results are robust to variation in key transmission model parameters within the range of their estimates from available literature. Infectious birds at the time of egg collection are a potential pathway of external contamination for eggs stored and then moved off of the farm; the predicted number of such infectious birds was estimated to be low. To date, there has been no evidence of vertical transmission of HPAI virus or low pathogenic avian influenza virus to day-old poults from hatching eggs originating from infected breeders. The application of risk analysis methods was beneficial for evaluating outbreak measures developed through emergency response planning initiatives that consider the managed movement of hatching eggs from monitored premises in an HPAI Control Area.

Spatial transmission of H5N2 highly pathogenic avian influenza between Minnesota poultry premises during the 2015 outbreak

The spatial spread of highly pathogenic avian influenza (HPAI) H5N2 during the 2015 outbreak in the U.S. state of Minnesota was analyzed through the estimation of a spatial transmission kernel, which quantifies the infection hazard an infectious premises poses to an uninfected premises some given distance away. Parameters were estimated using a maximum likelihood method for the entire outbreak as well as for two phases defined by the daily number of newly detected HPAI-positive premises. The results indicate both a strong dependence of the likelihood of transmission on distance and a significant distance-independent component of outbreak spread for the overall outbreak. The results further suggest that HPAI spread differed during the later phase of the outbreak. The estimated spatial transmission kernel was used to compare the Minnesota outbreak with previous HPAI outbreaks in the Netherlands and Italy to contextualize the Minnesota transmission kernel results and make additional inferences about HPAI transmission during the Minnesota outbreak. Lastly, the spatial transmission kernel was used to identify high risk areas for HPAI spread in Minnesota. Risk maps were also used to evaluate the potential impact of an early marketing strategy implemented by poultry producers in a county in Minnesota during the outbreak, with results providing evidence that the strategy was successful in reducing the potential for HPAI spread.

Quantifying the effect of swab pool size on the detection of influenza A viruses in broiler chickens and its implications for surveillance

BackgroundTimely diagnosis of influenza A virus infections is critical for outbreak control. Due to their rapidity and other logistical advantages, lateral flow immunoassays can support influenza A virus surveillance programs and here, their field performance was proactively assessed.The performance of real-time polymerase chain reaction and two lateral flow immunoassay kits (FluDETECT and VetScan) in detecting low pathogenicity influenza A virus in oropharyngeal swab samples from experimentally inoculated broiler chickens was evaluated and at a flock-level, different testing scenarios were analyzed.ResultsFor real-time polymerase chain reaction positive individual-swabs, FluDETECT respectively detected 37% and 58% for the H5 and H7 LPAIV compared to 28% and 42% for VetScan. The mean virus titer in H7 samples was higher than for H5 samples. For real-time polymerase chain reaction positive pooled swabs (containing one positive), detections by FluDETECT were significantly higher in the combined 5- and 6-swab samples compared to 11-swab samples. FluDETECT detected 58%, 55.1% and 44.9% for the H7 subtype and 28.3%, 34.0% and 24.6% for the H5 in pools of 5, 6 and 11 respectively.In our testing scenario analysis, at low flock-level LPAIV infection prevalence, testing pools of 11 detected slightly more infections while at higher prevalence, testing pools of 5 or 6 performed better. For highly pathogenic avian influenza virus, testing pools of 11 (versus 5 or 6) detected up to 5% more infections under the assumption of similar sensitivity across pools and detected less by 3% when its sensitivity was assumed to be lower.ConclusionsMuch as pooling a bigger number of swab samples increases the chances of having a positive swab included in the sample to be tested, this study’s outcomes indicate that this practice may actually reduce the chances of detecting the virus since it may result into lowering the virus titer of the pooled sample. Further analysis on whether having more than one positive swab in a pooled sample would result in increased sensitivity for low pathogenicity avian influenza virus is needed.