Melbourne School of Population and Global Health - Theses
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ItemVillage chicken production and the risk of avian influenza events in Indonesian villages( 2019)As of 2019, Highly Pathogenic Avian Influenza (HPAI) H5N1 is under control in Indonesia as a result of improved biosecurity and vaccination in large poultry enterprises. Nevertheless, the virus still circulates in less specialized village chicken production systems posing economic burden and public health risk. Past field research established that the trading activity associated with village chicken production is the primary pathway for HPAI-H5N1 release and spread in Indonesian villages; lamentably, the scarcity of data on village trading limits the exploration of risk frameworks to identify high-risk HPAI-H5N1 villages. This thesis investigates the village chicken productive landscape (that is, the collective of village chicken systems in a given village) as a determinant of the risk of HPAI-H5N1 events in Indonesian villages. Three core dimensions of these systems: type of village chicken system, village chicken productive dynamics, and risk mitigation strategies, are explored in relation to HPAI-H5N1 in four studies. First, a systematic review and meta-analysis that evaluates the efficacy of commercial vaccines against HPAI-H5N1 in Indonesia. Second, a Leslie matrix model to determine the underlying village chicken population dynamics and their effect on the maintenance of vaccine coverage. Third, an exploration and characterization of the Indonesian village chicken systems, along with the introduction of a deterministic age-structured model that simulates population dynamics and allows estimation of the presumed frequency of trading events to approximate the risk of HPAI-H5N1 release into villages. Fourth, a stochastic susceptible-exposed-infected age-structured model that allows exploration of transmission dynamics in different village chicken productive landscapes and evaluation of plausible risk mitigation strategies. The first study showed that viral drift reduces vaccine efficacy and that seed-homologous vaccine immunogenicity is not a good proxy for efficacy against wild isolates. The meta-analysis demonstrated that extra-label vaccination and the use of alternative seed homologous formulations are emerging sources of heterogeneous vaccine efficacy. The second study demonstrated that a mix of village chicken systems and not a "traditional scavenging" landscape, as suggested in the literature, drives the underlying village chicken population dynamics in Indonesia and these may quickly undermine perfect vaccine coverage. The third study demonstrated the limitations of the current classification of village chicken systems based on farming practice. The hierarchical clustering analysis in this study suggests that village chicken systems transitioned from traditional to semi-commercial modes of operation expressed as produce specialty (non-specialist, bird-specialist, or egg-specialists) and alternative trading strategies. The presumed frequency of trading events based on simulated productive dynamics suggests that the egg-specialists are heavily engaged in trading activities that increase the risk of HPAI-H5N1 release into villages. The fourth study shows that the type of village chicken landscape might not determine the probability of an epidemic event of HPAI-H5N1; however, outbreaks in landscapes that are abundant in bird-specialist and egg-specialist premises may persist longer. The simulations performed suggest that the extinction of the infected population seems invariably required to control these outbreaks. This thesis provides evidence that the Indonesian village chicken productive landscapes may determine the risk of HPAI-H5N1 events in Indonesian villages. This research suggests that a transition from traditional modes towards semi-commercial modes of operation that leads to a more significant presence of egg-specialists in the village results in a higher risk of viral release and likely more persistent epidemic events. The exploration of mitigation strategies which are plausible at the local level revealed challenges of controlling outbreaks in villages. These results emphasize the importance of identifying high-risk villages to enable adequate surveillance that reduces the need for mitigation strategies based on culling. In conclusion, this thesis suggests that an adequate characterization of the village chicken productive landscape may help, or even suffice, to identify villages at high risk of HPAI-H5N1 events, guiding surveillance, education, and future control efforts.
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ItemUnderstanding the determinants of pertussis spread to improve herd protection of vulnerable infants( 2014)In the first half of the 20th century, 2-5 yearly whooping cough epidemics caused a substantial burden of death and disease in Australia. The introduction of mass vaccination in the 1950s dramatically reduced disease incidence, but from the 1980s onwards resurgence of cases was observed, placing vulnerable infants at risk. Similarly to other countries with well-established vaccine programs, from 2008-2012 pertussis incidence reached the highest levels in Australia since the implementation of vaccination. I developed an age structured, deterministic, compartmental transmission model to investigate the underlying infection patterns consistent with Australia's observed pertussis epidemiology, using a variety of local data resources. Varying levels of susceptibility to infection were included to account for the possible dependence of susceptibility and infection characteristics on the time since prior infection or vaccination. Biologically plausible parameter ranges were explored using Latin Hypercube Sampling and the model simulated through the pre-vaccine and vaccine eras. Simulation results were filtered to match aspects of pertussis epidemiology about which we can be reasonably certain from long term surveillance data, including persistence of 2-5 year epidemic cycles, relative maintenance of infant protection and declining natural immunity across all age cohorts. Only simulations with natural immunity lasting decades simultaneously reproduced the adult immunity profiles observed in serosurveillance and the substantial impact of vaccination on incidence. Although the initial impact of vaccination was substantial, fluctuations in vaccination coverage through the pertussis vaccine scare of the 1970s were sufficient to allow breakthrough increases in circulation in the model. The long duration of natural immunity required to match observed epidemiology meant that cohorts infected during periods of low coverage were primed to experience a resurgence decades later. In order to replicate the observed sustained, substantial impact of vaccination on infants, the model had to be configured with the primary course delivered as three separate doses, with additional protection against infection acquired with each dose. This finding was consistent with the reduction in infant disease observed across the 2, 4 and 6 month schedule age points. Additionally, an emergent property of the model was that pertussis vaccines induce herd protection of infants. Using my model to project alternative historical vaccination schedules for simulations matching the key characteristics of pertussis in Australia, I found that of the changes made after 1990, the addition of the pre-school booster in 1995 had the largest impact on infection incidence in infants. While the replacement of the 18mth booster with an adolescent dose from 2003 had a limited impact on infants, the direct effect on the 18mth-4yr age group was substantial. More generally, the addition of extra doses to the vaccine schedule increased herd protection in the model, while altering the ages at which doses are given had substantial direct effects but a limited impact on infants. The challenge for policy makers is to design a vaccine program that allows circulation sufficient to maintain immunity in older age groups through boosting while simultaneously protecting infants from such circulation.