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1.  Simulation-guided design of serological surveys of the cumulative incidence of influenza infection 
BMC Infectious Diseases  2014;14(1):505.
Influenza infection does not always cause clinical illnesses, so serological surveillance has been used to determine the true burden of influenza outbreaks. This study investigates the accuracy of measuring cumulative incidence of influenza infection using different serological survey designs.
We used a simple transmission model to simulate a typical influenza epidemic and obtained the seroprevalence over time. We also constructed four illustrative scenarios for baseline levels of antibodies prior and levels of boosting following infection in the simulated studies. Although illustrative, three of the four scenarios were based on the most detailed empirical data available. We used standard analytical methods to calculate estimated seroprevalence and associated confidence intervals for each of the four scenarios for both cross-sectional and longitudinal study designs. We tested the sensitivity of our results to changes in the sampled size and in our ability to detect small changes in antibody levels.
There were substantial differences between the background antibody titres and levels of boosting within three of our illustrative scenarios which were based on empirical data. These differences propagated through to different and substantial patterns of bias for all scenarios other than those with very low background titre and high levels of boosting. The two survey designs result in similar seroprevalence estimates in general under these scenarios, but when background immunity was high, simulated cross-sectional studies had higher biases. Sensitivity analyses indicated that an ability to accurately detect low levels of antibody boosting within paired sera would substantially improve the performance of serological surveys, even under difficult conditions.
Levels of boosting and background immunity significantly affect the accuracy of seroprevalence estimations, and depending on these levels of immunity responses, different survey designs should be used to estimate seroprevalences. These results suggest that under current measurement criteria, cumulative incidence measured by serological surveys might have been substantially underestimated by failing to include all infections, including mild and asymptomatic infections, in certain scenarios. Dilution protocols more highly resolved than serial 2-fold dilution should be considered for serological surveys.
PMCID: PMC4261848  PMID: 25231414
Infection attack rate; Cumulative incidence; Seroprevalence; Influenza; Serological survey; Cross-sectional study design; Longitudinal study design; Mathmatical modelling
2.  Surveillance of low pathogenic novel H7N9 avian influenza in commercial poultry barns: detection of outbreaks and estimation of virus introduction time 
BMC Infectious Diseases  2014;14(1):427.
Both high and low pathogenic subtype A avian influenza remain ongoing threats to the commercial poultry industry globally. The emergence of a novel low pathogenic H7N9 lineage in China presents itself as a new concern to both human and animal health and may necessitate additional surveillance in commercial poultry operations in affected regions.
Sampling data was simulated using a mechanistic model of H7N9 influenza transmission within commercial poultry barns together with a stochastic observation process. Parameters were estimated using maximum likelihood. We assessed the probability of detecting an outbreak at time of slaughter using both real-time polymerase chain reaction (rt-PCR) and a hemagglutinin inhibition assay (HI assay) before considering more intense sampling prior to slaughter. The day of virus introduction and R0 were estimated jointly from weekly flock sampling data. For scenarios where R0 was known, we estimated the day of virus introduction into a barn under different sampling frequencies.
If birds were tested at time of slaughter, there was a higher probability of detecting evidence of an outbreak using an HI assay compared to rt-PCR, except when the virus was introduced <2 weeks before time of slaughter. Prior to the initial detection of infection Nsample = 50 (1%) of birds were sampled on a weekly basis once, but after infection was detected, Nsample = 2000 birds (40%) were sampled to estimate both parameters. We accurately estimated the day of virus introduction in isolation with weekly and 2-weekly sampling.
A strong sampling effort would be required to infer both the day of virus introduction and R0. Such a sampling effort would not be required to estimate the day of virus introduction alone once R0 was known, and sampling Nsample = 50 of birds in the flock on a weekly or 2 weekly basis would be sufficient.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2334-14-427) contains supplementary material, which is available to authorized users.
PMCID: PMC4129106  PMID: 25085078
H7N9; Influenza; Surveillance; R0; Poultry
3.  Minimizing the threat of pandemic emergence from avian influenza in poultry systems 
BMC Infectious Diseases  2013;13:592.
Live-animal markets are a culturally important feature of meat distribution chains in many populations, yet they provide an opportunity for the maintenance and transmission of potentially emergent zoonotic pathogens. The ongoing human outbreak of avian H7N9 in China highlights the need for increased surveillance and control in these live-bird markets (LBMs).
Closure of retail markets in affected areas rapidly decreased human cases to rare, sporadic occurrence, but little attention has been paid thus far to the role of upstream elements of the poultry distribution chain such as wholesale markets. This could partly explain why transmission in poultry populations has not been eliminated more broadly. We present surveillance data from both wholesale live-bird markets (wLBMs) and rLBMs in Shantou, China (from 2004–2006), and call on disease-dynamic theory to illustrate why closing rLBMs has only minor effects on the overall volume of transmission. We show that the length of time birds stay in rLBMs can severely limit transmission there, but that the system-wide effect may be reduced substantially by high levels of transmission upstream of retail markets.
Management plans that minimize transmission throughout the entire poultry supply chain are essential for minimizing exposure to the public. These include reducing stay-time of birds in markets to 1 day, standardizing poultry supply chains to limit transmission in pre-retail settings, and monitoring strains with epidemiological traits that pose a high risk of emergence. These actions will further limit human exposure to extant viruses and reduce the likelihood of the emergence of novel strains by decreasing the overall volume of transmission.
PMCID: PMC3878446  PMID: 24341669
Avian influenza; Live-bird markets; Efficacy of controls; Environmental transmission; Wholesale markets
4.  Entry screening to delay local transmission of 2009 pandemic influenza A (H1N1) 
After the WHO issued the global alert for 2009 pandemic influenza A (H1N1), many national health agencies began to screen travelers on entry in airports, ports and border crossings to try to delay local transmission.
We reviewed entry screening policies adopted by different nations and ascertained dates of official report of the first laboratory-confirmed imported H1N1 case and the first laboratory-confirmed untraceable or 'local' H1N1 case.
Implementation of entry screening policies was associated with on average additional 7-12 day delays in local transmission compared to nations that did not implement entry screening, with lower bounds of 95% confidence intervals consistent with no additional delays and upper bounds extending to 20-30 day additional delays.
Entry screening may lead to short-term delays in local transmission of a novel strain of influenza virus. The resources required for implementation should be balanced against the expected benefits of entry screening.
PMCID: PMC3152767  PMID: 20353566

Results 1-4 (4)