This PhD thesis aimed at evaluating the contribution of participatory epidemiology (PE) to improve the foot-and-mouth disease (FMD) surveillance and control activities, especially the involvement of farmers at local level. The first objective aimed at assessing the effectiveness of the FMD surveillance and vaccination strategy at local level by using PE approach. The second objective aimed at assessing the feasibility of applying PE tools to improve the involvement of farmers in the FMD surveillance in Vietnam. PE methods performed in our study included informal interviews (focus group and individual), scoring tools (pairwise ranking, proportional pilling, disease impact matrix scoring and disease signs matrix scoring), visualization tools (mapping, timeline, flow chart) and sociological tools called Q methodology. 122 focus groups, 467 individual interviews, 339 questionnaire surveys were performed during two field studies in 2014 and 2015. 409 sera and 152 probang samples were taken. Conventional questionnaire surveys, Bayesian modelling and laboratory test (ELISA and rtRT-PCR) was used to validate the performance of PE in FMD surveillance. Disease was considered as the most important issues in animal production. FMD was the most important disease for dairy cattle production, followed by haemorrhagic septicaemia. For beef cattle production, it was recorded in reverse order. The most important disease for pig production was porcine reproductive and respiratory syndrome while FMD was ranked fourth. Farmers showed their abilities in differential diagnostic of important diseases based on its clinical symptoms. Sero-prevalence of FMD were estimated at 23% for population 1 (bordering with Cambodia) and 31% for population 2 (locating far from the border), respectively. Sensitivity and Specificity of PE were found to be 59% and 81%, respectively. The positive and negative predictive value were found to be 48% and 86% for population 1 and 58% and 81% for population 2, respectively. The presence of serotype A, lineage A/Asia/Sea-97 and serotype O with two separate lineages, O/ME-SA/PanAsia and O/SEA/Mya-98 supported virus circulation through trans-boundary animal movement activities. Dairy farms frequently applied quarantine, disinfection and vaccination as prevention methods. Beef farms preferred cleanliness and good husbandry management practices. Pig farms considered that all prevention methods had the same importance. Three distinct discourses “Believe”, “Confidence”, “Challenge”, representing common perceptions among farmers and accounting for 57.3 % of the variance, were identified based on Q methodology. Farmers take vaccination decisions themselves without being influenced by other stakeholders and feel more secure after FMD vaccination campaigns. However, part of the studied population did not consider vaccination to be the first choice of prevention strategy. The benefitcost ratio of FMD vaccination for dairy cow production in large-scale and in small-scale and meat cattle production were 37.2, 30.0 and 7.3, respectively. The sensibility analysis showed that FMD vaccination was profitable for all of production types even through the increase of vaccine cost and decrease of market price of milk and slaughter cattle. From the focus groups organized at sentinel villages, 18 new villages were identified as potentially infected by FMD. 77 suspected animals were confirmed positive for FMD, with viral serotypes O and A. Sensitivity and specificity of participatory surveillance were recorded at 0.75 and 0.65, respectively. The effectiveness of PE in FMD surveillance system to detect outbreak in Vietnam was demonstrated. It was demonstrated that vaccination was the most effective and economic method to prevent FMD. Through the application of simple, adaptive tools which facilitate direct and active participation of farmers, PE allowed to reach a better acceptability of surveillance and to obtain qualified information.

The thermostability of vaccines is of crucial importance in Africa, where the logistical process to get the vaccine from the manufacturer to the animal may take months, and in many remote regions transport and storage is in the absence of a cold-chain. Vaccines with improved stability and less reliance on a cold-chain are needed and could improve the longevity of immune responses elicited in vaccinated animals. In South Africa, cattle in the vaccination zone neighbouring the Kruger National Park have to be vaccinated thrice annually because of declining antibody responses at three months postvaccination. FMDV is known to be unstable, especially for O and SAT2 serotypes in mildly acidic pH conditions or at elevated temperatures, leading to dissociation of the capsid (146S particle) and loss of immunogenicity. The link between rapidly declining antibody responses and capsid stability have been reported by Doel and Baccarini, 1981. We hypothesized that more stable viruses, especially thermostability, will not only improve the protective immune response in animals but also require less frequent booster vaccinations. / The residues at the capsid inter-pentamer interfaces, and their interactions, are important for the infectivity and stability of the virion and mutations adjacent to these interfaces have an effect on the conformational stability of FMDV. However, experimental studies on the relative importance of residues and molecular interactions in viral capsid assembly, disassembly, and/or stability are still very limited, especially for the SAT serotypes of FMDV. This study investigated the effects of potential residues at the pentameric interfaces that are responsible for increased thermostability and potentially improved stability candidates were tested in small (guinea pigs) and large (cattle) animal vaccination trials to understand the role of stabilised antigens on immune responses. The biological variation in biophysical stability in SAT2 viruses in the southern Africa region was investigated to determine if any naturally occurring viruses have greater capsid thermostability. Naturally occurring stable viruses could be used as prospective candidates in vaccine production and therefore potentially result in increased duration of immune responses. / Our first aim was to investigate the role of different amino acid changes at the interface and their effect on capsid stability using models derived by Oxford University. These changes were introduced by mutating the SAT2 ZIM7/83 infectious genome-length clone (pSAT2) to derive mutated chimeric SAT2 viruses. We quantified the stabilizing effects of these mutations by using various stability assays. We established the novel thermofluor shift assay that is able to quantify the capsid stability of viruses. The growth kinetics, antigenicity, genetic stability, pH and salt sensitivity were investigated for each of the genetically engineered viruses (Chapters 2 and 3). / The second aim was to further our understanding on the correlation between improved stability and immune responses by performing small animal (Chapter 2) and large animals trials in cattle (Chapter 4) and comparing stabilised and wild-type antigens. This study for the first time for SAT vaccines, determined differences in IgG1 and IgG2 profiles, interferon gamma (IFN-γ) responses and differences in total and neutralising antibodies of stabilised and wild-type antigens over a six month period in cattle (Chapter 4). Animals were intra-dermolingually challenged with live virus to determine levels of protection the antigens have afforded. / In addition, a third aim will be to better understand the inherent thermostability variation of SAT2 viruses in the Southern African region (Chapter 5) by establishing a protocol for screening field isolates as potential vaccine strains and correlating their stability to amino acid residues at the interface of the 146S particles. / Thesis (PhD)--University of Pretoria, 2016. / Agricultural Research Council / Veterinary Tropical Diseases / PhD / Unrestricted

Within East African countries many of the known infectious diseases of animals occur commonly and are poorly controlled. Foot-and-mouth disease (FMD) is one of the contagious viral diseases that has great impact on economic development both in terms of direct and indirect losses. The epidemiology of the disease is complex due to the presence of six of the seven serotypes and the presence of large numbers of both wild and domestic susceptible animals in the region. Decision-making to determine the importance of FMD control relative to the economic consequences and what FMD control strategies should be applied based on the epidemiological information is required. In this regard the first step is to investigate the genetic relationships/variability of East African isolates and their phylogeographic distribution. These can provide base-line information for designing control strategies by vaccination as well as the determination of the sources of infection. Sufficient genetic information on the FMO serotypes O, SAT-1 and SAT-2 are lacking and therefore the number of viral Iineages and genotypes or topotypes from East African countries could not be determined. Published studies on the relative occurrence and genotype distribution of FMO are largely confined to the southern and western part of the continent. In this study, the genetic profile of the 3 most prevalent serotypes (0, SAT-2 and SAT-1) recovered from outbreaks in East Africa between 1957 and 2003 was addressed. Phylogenetic analysis of partial and complete sequences of the 10 gene revealed the presence of distinct lineages and genotypes for East Africa as well as historical relationships of some of the genotypes with isolates from other regions. A great variation in the occurrence and distribution of these serotypes were found. All the African and the Middle East/South East Asian isolates of serotype O included in this study clustered into one lineage having 8 distinct topotypes. These results indicated that between countries as well as inter-regional (east and west Africa) spread of viruses occurred in the past. Inter-regional spread of the virus between eastern Africa and western Africa was also confirmed for SAT-1 viruses. The fact that phylogenetic links are found with both serotypes implies that the spread of viruses was possibly associated with unrestricted animal movement due to nomadic movement in Africa. The phylogenetic relationships of SAT-1 viruses are more diversified in Africa. Eight lineages and 11 genotypes were identified when the optimal nucleotide sequence differences of ≥ 23% for lineages and ≥ 6% for genotypes were used as a cut-off values. It was observed that viruses from Uganda are evolving independently from viruses elsewhere on the continent and clustered into 3 discrete lineages. In contrast, viruses from countries neighbouring Uganda, Kenya and Tanzania, clustered into one lineage. Uganda also harboured 3 topotypes of SAT-2 virus isolates, one is distinct for Uganda and the other are shared with Kenya and Zaire (DRC). This study highlighted distinct lineages found in Uganda and needs further investigation. Within SAT-2, 67 isolates from 22 African countries and Saudi Arabia clustered into 5 lineages which consisted of 15 genotypes. Clustering of viruses into distinct genotypes (topotypes) according to year of isolation and geographical origin was observed showing countries with common boundaries shared common epizootics in the past. These results also showed a link between eastern and southern African countries. Attempts were also made to investigate the incidence of FMD in Ethiopia using sera collected from cattle, small ruminants and wildlife. The results obtained from the liquid phase blocking ELISA and the 3ABC ELISA indicated the presence of SAT-1 and SAT-2 in buffalo populations in the southern part of Ethiopia while results from small ruminants and other wildlife were not indicative of any significant role in the epidemiology of FMD. Serological results also indicated that SAT-1 is present in cattle, although this serotype has not been previously identified. The cumulative molecular epidemiological results from this and previous studies indicated that genetic variability of FMD viruses can be independently maintained within country/countries or regions as well as inter-regions of Africa. The serological results from buffaloes in East Africa are also suggestive of a possible reservoir of the SAT types FMD in the region which has a great impact on the control of the disease. Furthermore, the numerous lineages and genotypes of FMD virus isolates in Africa having distinct or overlapping distributions as well as the genetic linkage between regions will complicate the epidemiology of the disease. Therefore, it is strategically important to consider a regional approach and the use of a vaccine which contains a cocktails of antigens of FMD virus strains. / Thesis (PhD)--University of Pretoria, 2004. / Veterinary Tropical Diseases / unrestricted

Food safety scares affect consumption behavior, and food safety and animal health issues are increasingly impacting international agricultural trade. Foot-and-mouth disease (FMD) is a highly contagious viral-type disease, and has raised not only the concerns of animal health issue but also food safety issue. Over 58 countries in the world have experienced FMD outbreaks, and pork exports and imports among these countries are largely impacted. This dissertation focuses on how global pork trade is affected by FMD. This dissertation consists of three parts: first, this study specifically focuses on the market of U.S. pork exports. Results show that disease-affected pork importers are potential traders with the U.S., and only importing countries with a vaccination policy are more likely to increase pork imports from the U.S. rather than those importers with a slaughter policy. Second, a further investigation focuses basic hypothesis on import demand of FMD-affected importers by using a gravity model with fixed-effects to show how pork trade is affected by FMD among 186 countries. Results confirm that pork export falls when an exporting country develops FMD. Exporters with a vaccination policy have larger negative impacts than those with a slaughter policy. Further, pork importers that develop FMD and institute a slaughter policy will import more pork, but importers with a vaccination policy import the same level of pork. Third, the findings of part one and two reveal that FMD-free pork exporters face different market opportunities when pork importers have FMD outbreaks. Hence, four major FMD-free pork exporters, such as Canada, U.S., Germany, and Spain, are further investigated. Results confirm that the impacts of foreign FMD have altered pork exporters differently. Germany has gained the most exports during foreign FMD outbreaks in pork importers; the U.S. is second; Spain is third; and Canada is fourth. In sum, this dissertation contributes to the literature of gravity model when endogeneity and heteroskedasticity may coexist, when an extremely large number of zero observations are included, when single commodity for one specific exporter is analyzed, when a spatial econometric approach is compared, and when pork export market has been altered by foreign FMD outbreaks.

During 2007 the UK experienced outbreaks of three notifiable exotic livestock diseases; Foot and Mouth Disease (FMD), Highly Pathogenic Avian Influenza (HPAI) and bluetongue. Large epidemics of any of these diseases would have a serious impact on animal welfare, farming, food production and the economy. In light of this, understanding holdings which are most likely to acquire and spread infection and being able to identify areas at higher risk of an epidemic is valuable when preparing for and managing an epidemic. This thesis uses a spatial epidemiological framework and the detailed disease and demographic data from the 2001 Great Britain (GB) FMD epidemic to develop static models of the risk of FMD susceptibility and transmission. These models are used to develop maps of FMD risk. These methods are then applied to the outbreak of FMD in 2007. The inputs for this analysis comprised a set of data relating to the farms diagnosed with FMD and farms culled as part of the disease control measures. The cleaning of these data is described and data which were estimated relating to dates of infection and putative sources of infection are evaluated. The distribution of farm holdings and animals is taken from the June 2000 GB agricultural census, off-fields of farms in the agricultural census are recorded in other datasets and these have been identified and linked to census holdings. A model of holding level susceptibility is developed using both farm level variables and measures of animal numbers in the locality of the holding as well as the distance to the nearest farm infected before the ban on animal movements (seeds). The overall fit of the model was very good with an area under the Receiver Operator Characteristic (ROC) curve of 0.91. A further model was developed to describe the risk of FMD transmission. However, due to incompleteness of transmission data, this was a model of the risk of finding a subsequent Infected Premises (IP) within 3km of an IP. Risk factors were a combination of holding level variables and locality measures as well as data relevant to the infection, such as infectious period and the species initially infected. The area under the ROC curve for this model was 0.71, which is regarded as an acceptable fit. Geographical barriers to FMD transmission were investigated using a case-control methodology, linear barriers comprising rivers and railways had a significant protective effect with respect to disease transmission (odds ratio = 0.54, 95% CIs = 0.30,0.96, p=0.038). Modelled values for the transmission and susceptibility models were transformed to a raster surface in ESRI ArcMap for both the disease as it was seeded in the 2001 epidemic and a non-specific background risk surface independent of the distribution of seeds. A risk map generated for the outbreak of FMD in Surrey in August 2007 suggested that there was little risk of a large outbreak in Surrey. Potential disease introductions through livestock movements from Surrey into Scotland were identified and these suggested that if the disease were introduced into Scotland there was great danger of substantial local spread. These methods described in this thesis have been used to map risk of FMD and subsequently applied to inform the risk presented by a different outbreak of FMD. The study underlines the value of detailed data both disease and demographic, for epidemic management. Similar methods could and should be applied to other infectious diseases threats of livestock such as HPAI and bluetongue.

Doctor of Philosophy / Department of Diagnostic Medicine and Pathobiology / Michael W. Sanderson / The last outbreak for Foot and Mouth Disease (FMD) in the United States (U.S.) was in 1929. Since that time the U.S. has not had any exposure to the disease or vaccination, creating a very susceptible livestock population. The central U.S. has a large susceptible livestock population including cattle, swine, sheep, and goats. The impact of FMD in the U.S. would be devastating. Simulation modeling is the only avenue available to study the potential impacts of an introduction in the U.S. Simulation models are dependent on accurate estimates of the frequency and distance distribution of contacts between livestock operations to provide valid model results for planning and decision making including the relative importance of different control strategies. Due to limited data on livestock movement rates and distance distribution for contacts a survey was conducted of livestock producers in Colorado and Kansas. These data fill a need for region specific contact rates to provide parameters for modeling a foreign animal disease. FMD outbreaks often require quarantine, depopulation and disposal of whole herds in order to prevent the continued spread of the disease. Experts were included in a Delphi survey and round table discussion to critically evaluate the feasibility of depopulating a large feedlot. No clearly acceptable method of rapidly depopulating a large feedlot was identified. Participants agreed that regardless of the method used for depopulation of cattle in a large feedlot, it would be very difficult to complete the task quickly, humanely, and be able to dispose of the carcasses in a timely fashion. Simulation models were developed to assess the impact of livestock herd types and vaccination on FMD outbreaks in the central U.S. using the North American Animal Disease Spread Model (NAADSM), a spatially explicit, stochastic state-transition simulation model. Simulation scenarios with large vaccination zones had decreased outbreak length and number of herds destroyed. Vaccination did not provide additional benefit to control compared to depopulation alone when biosecurity and movement controls were high, however the ability to achieve high levels of biosecurity and movement control may be limited by labor and animal welfare concerns.

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2017-06-09T17:31:45Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) ALESSANDRA ARANDA GAVIAO.pdf: 1650079 bytes, checksum: 0968c238fcfd9ba854ff63559a71860c (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2017-06-09T17:31:59Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) ALESSANDRA ARANDA GAVIAO.pdf: 1650079 bytes, checksum: 0968c238fcfd9ba854ff63559a71860c (MD5) / Made available in DSpace on 2017-06-09T17:31:59Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) ALESSANDRA ARANDA GAVIAO.pdf: 1650079 bytes, checksum: 0968c238fcfd9ba854ff63559a71860c (MD5) Previous issue date: 2017-03-01 / A febre aftosa (FMD) é economicamente a doença mais importante de biungulados e a ocorrência de um surto produz repercussões nacionais e internacionais. O vírus da febre aftosa (FMDV), agente causal, é extremamente infeccioso e contagioso. A infecção afeta principalmente bovinos, bubalinos, suínos, ovinos, caprinos entre outras espécies domésticas e silvestres. O controle da enfermidade é realizado pelo rápido diagnóstico, vacinação preventiva e restrição da movimentação de animal. Assim sendo, as medidas de controle são direcionadas em medidas de prevenção, que incluem vigilância ativa e passiva. O último surto de FMDV no Rio Grande do Sul ocorreu em 2001 e atualmente o estado é reconhecido como zona livre com vacinação. Para que o Estado mantenha este status, faz-se necessário um sistema de vigilância eficaz capaz de integrar o Serviço Veterinário Oficial (SVO) e a cadeia produtiva (diferentes agentes envolvidos). O objetivo deste estudo foi avaliar a percepção de risco dos produtores, médicos veterinários e transportadores de bovinos da cadeia produtiva na Fronteira Oeste do Rio Grande do Sul. Todos os atores entrevistados reconhecem a importância da febre aftosa. No entanto, uma parcela dos produtores (15%), transportadores (17%) e veterinários (17%) acredita que a doença ocorra no Estado. Também uma quantia considerável de produtores e transportadores acredita que o risco de o vírus ser introduzido na região seja baixo, desprezível e alguns ainda não souberam responder. Observou-se que os entrevistados reconhecem os principais sinais clínicos, porém possuem pouco conhecimento quanto a ovinos, suínos, cervos e porcos selvagens serem suscetíveis a febre aftosa. Grande parte dos entrevistados acredita ser importante comunicar um caso suspeito, porém uma parcela tentaria resolver de outra maneira, caso suspeitasse da doença. Quase a totalidade dos produtores afirmou vacinar seus rebanhos, no entanto alguns possuem conhecimento de produtores que não realizam a vacinação. Além disso, alguns entrevistados não sabem a idade inicial para realizar a vacinação. Dessa forma, é de extrema importância o Serviço Veterinário Oficial atuar com mais intensidade em atividades de educação sanitária, no que diz respeito a idade correta para vacinação, as espécies afetadas e a notificação, tornando os atores mais sensíveis a qualquer suspeita da doença. / Foot-and-mouth disease (FMD) is the most important animal disease and the occurrence of an outbreak has national and international repercussions. Foot-and-mouth disease virus (FMDV), the causative agent, is extremely infectious and contagious. The infection mainly affects cattle, buffaloes, swine, sheep, goats among other domestic and wild species. Disease control is performed by a fast diagnosis, preventive vaccination and restriction of animal movement. Therefore, control measures are directed at prevention measures, which include active and passive surveillance. The last FMDV outbreak in Rio Grande do Sul occurred in 2001 and the State is recognized as a free zone with vaccination. In order for the State to maintain this status, an effective surveillance system capable of integrating the Official Veterinary Service and the production chain (producers and handlers) is necessary. The objective of this study was to evaluate the risk perception of producers, veterinarians and cattle transporters in the production chain in the West Frontier of Rio Grande do Sul, Brazil. All interviewed actors recognize the importance of foot-and-mouth disease. However, a proportion of the producers (15%), transporters (17%) and veterinarians (17%) believe that the disease occurs in the State. Also, a considerable number of producers and transporters believe that the risk of the virus being introduced in the region is low, negligible and some have not yet been able to respond. It was observed that the interviewees recognize the main clinical signs, but they have little knowledge about sheep, pigs, deer and wild pigs being susceptible to foot-and-mouth disease. Most interviewees believe it is important to report a suspected case, but a portion would try to solve it differently if they suspected the disease. Almost all producers claimed to vaccinate their herds, however some are aware of producers who do not carry out the vaccination. In addition, some interviewees do not know the starting age to carry out the vaccination. Therefore, it is extremely important for the Official Veterinary Service to work with more intensity in health education activities, regarding the correct age for vaccination, affected species and notification, making the actors more sensitive to any suspicion of the disease.

Background / Hand, foot, and mouth disease (HFMD), in particular those associated with enterovirus 71 (EV71), has caused large outbreaks in the Western Pacific and Southeast Asian countries in the past three decades. There is currently no effective chemoprophylaxis or vaccination for HFMD or EV71 infection. Public health strategies rest on good understanding of the epidemiological features of HFMD. The present series of studies examined the epidemiological characteristics of HFMD in Hong Kong, with a view to better understand the disease epidemiology so as to guide public health actions. / Methods and results of individual studies / Study (1)--characterizing the changing epidemiological features identified from various surveillance systems for HFMD / The trend of HFMD activities from 2001-2009 was analyzed using the sentinel surveillance statistics and HFMD outbreaks. The type of institutions reporting HFMD over time, incidences of outbreaks in 18 districts, and age and sex distribution of affected persons of HFMD outbreaks were analyzed. The clinical presentation, hospitalization rate, complication rate and case fatality of outbreaks were examined. The circulating enterovirues each year were determined by laboratory surveillance findings from 2001-2009 and test for morbidity caused by EV71. Seasonal peak was detected from warmer months of May through July but a smaller winter peak was found from October to December since 2006. An increasing trend of more older children aged above 5 years were infected, from 25.4% in 2001 to 33.0% in 2009 (p=0.01, Mantel-Haenszel Chi-square test). Laboratory surveillance detected a cyclical high activity of EV71 in every 3 to 4 years, which was associated with a higher average hospitalization rate among patients of the HFMD outbreaks reported in corresponding year, although it was only marginally significant (p=0.09, linear regression test). / Study (2)--analyzing the characteristics of EV71 epidemic in 2008 / All EV71 cases diagnosed by PHLC from 1998-2008 were analyzed. The complication and case fatality rates, percentage requiring hospitalization, median duration of hospital care, and the likelihood of being associated with an HMFD outbreak in institution in 2008 were compared with the corresponding rates calculated from cases reported from 1998-2007. Phylogenetic tree was constructed by using the neighbour-joining method and the molecular epidemiology of EV71 detected in 2008 was compared with the past years’ trends. Ninety-eight EV71 cases were reported in 2008, highest in the past decade. The annual incidence was 1.4/100 000 in general population, with highest incidence reported in children aged 0-4 years old (27.9/100 000). 11.2% had complications including meningitis or encephalitis (6.1%), pneumonia (3.1%), acute flaccid paralysis (1.0%), and shock (1.0%). There was only one fatal case (CFR: 1.0%) attributed to interstitial pneumonitis. 45.9% had concurrent HFMD outbreaks in their schools or institutions, and six schools required temporarily class suspension for 14 days. Both the complication rate and CFR werenot significantly different from the corresponding rates of the past 10 years (p=0.12 and 1.00 respectively). Phylogenetic analysis found that most cases reported in 2008 were C4 strains, which were the predominant circulating strains in the past ten years. / Study (3)--examining the association between meteorological parameters and HFMD activity / The sentinel consultation rate of HFMD was tested for any association with the meteorological parameters obtained from the Hong Kong Observatory from 2000-2004. Different regression models were examined to find the best model for predicting HFMD consultation rates from 2005-2009. In multivariate regression analysis, model M2 (in which mean temperature, diurnal difference in temperature, relative humidity and wind speed were positively associated with HFMD) was found to have a higher R2 (0.119) than M0 and M1 models with an R2 of 0.079 and 0.062 respectively, indicating that HFMD consultation rates were better explained using meteorological parameters measured 2 weeks earlier. The predicted trend of HFMD consultation rates for 2005 to 2009 matched well with the observed one (Spearman’s rank correlation coefficient=0.276, P=0.000). Sensitivity analysis showed that the estimated HFMD consultation rates were mostly affected by varying the relative humidity and least affected by wind speed. / Study (4)--determining the basic reproduction number of coxsackievirus A16 and enterovirus 71 using mathematical model / The basic reproduction numbers (R0) of EV71 and CoxA16 from laboratory confirmed HFMD outbreaks reported to DH from 2004-2009 were determined using mathematical model. Thirty four outbreaks were analyzed, 27 due to CoxA16 and seven due to EV71. The median R0 of EV71 was 5.48 with an inter-quartile range of 4.206.51 while median R0 of CoxA16 was 2.50 with an inter-quartile range of 1.963.67. In the sensitivity analysis, R0 of EV71 was significantly higher than that of CoxA16 in whole range of incubation periods, p≦0.025. R0was not associated with outbreak setting, size of the institution or number of persons affected. / Study (5)--assessing the impact of SARS and pandemic influenza H1N1 on transmission of HFMD in Hong Kong / I compared the observed HFMD consultation rates and the projected rates, which were constructed using mathematical model, in defined periods of 2003 and 2009 during which territory-wide public health interventions (including school closure) against Severe Acute Respiratory Syndrome (SARS) and pandemic influenza H1N1 were implemented. There was a reduction of 57.2% (95% C.I.:53.0-60.7%) in observed HFMD consultation rates during SARS period in 2003 and a reduction of 26.7% (95% C.I.:19.5-32.7%) during pandemic influenza H1N1 period in 2009. In 2003, the projected rates were still lower than the observed rates beyond week 31 until almost the end of the year. On the contrary, in 2009, the observed HFMD consultation rates became comparable to that of the projected rates in August, before the end of the defined intervention period. / Conclusions / This thesis bridges the knowledge gaps regarding epidemiological characteristics of HFMD. The changing epidemiology of HFMD, including the cyclical high activity of EV71 warrants vigilant surveillance of its activity in order to guide preventive measures. I have demonstrated that climate parameters may help predict HFMD activity, which could assist in explaining the winter peak detected in recent years and issuing early warning in the future. The R0 of EV71 and CoxA16 were first determined in the literature and I found that R0 of EV71 was higher than R0 of CoxA16. The reduction of transmission of HFMD during the SARS and H1N1 periods suggested that public health measures are effective in reducing the transmission of enteroviruses. / Ma, Siu Keung. / Thesis (M.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 121-149). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Table of content --- p.ii / Acknowledgements --- p.iv / Abbreviations --- p.v / Caption for Tables --- p.vi / Caption for Figures --- p.viii / Précis --- p.1 / Chapter PART I: --- LITERATURE REVIEW ON HFMD --- p.5 / Chapter Chapter 1. --- Current Understanding of Epidemiology of HFMD --- p.6 / Chapter 1.1 --- Causative agents and virology --- p.6 / Chapter 1.2 --- Clinical presentation and management --- p.8 / Chapter 1.3 --- Geographical distribution and past epidemics --- p.14 / Chapter 1.4 --- Host susceptibility and molecular determinants of neruovirulence --- p.26 / Chapter 1.5 --- Routes of transmission and transmission dynamics --- p.27 / Chapter 1.6 --- Knowledge gap identified from literature review --- p.29 / Chapter PART II: --- STUDIES ON EPIDEMIOLOGY OF HFMD IN HONG KONG --- p.33 / Chapter Chapter 2. --- Study Objectives and Main data source for analysis --- p.34 / Chapter 2.1 --- Aim and objectives of this thesis --- p.34 / Chapter 2.2 --- Sentinel surveillance system for monitoring HFMD activity --- p.35 / Chapter 2.3 --- Institutional outbreaks of HFMD reported to DH . --- p.37 / Chapter 2.4 --- EV 71 infection reported to Department of Health --- p.37 / Chapter 2.5 --- Laboratory surveillance for monitoring enteroviruses --- p.37 / Chapter Chapter 3. --- Study (1)--Characterizing the changing epidemiological features identified from various surveillance systems for HFMD --- p.38 / Chapter Chapter 4. --- Study (2)--Analyzing the epidemic of enterovirus 71 in 2008 and its public health implication to Hong Kong --- p.52 / Chapter Chapter 5. --- Study (3)--Examining the association between meteorological parameters and HFMD activity --- p.67 / Chapter Chapter 6. --- Study (4)--Determining the basic reproduction number of coxsackievirus A16 and enterovirus 71 using mathematical model --- p.85 / Chapter Chapter 7. --- Study (5)--Impact of SARS and Pandemic Influenza H1N1 on transmission of HFMD in Hong Kong --- p.100 / Chapter Chapter 8. --- Conclusion --- p.111 / List of publications related to this thesis --- p.119 / References --- p.121

Merino sheep are the most numerous domestic livestock in Australia and feral goats are wide-spread and locally abundant in many of the regions where sheep are grazed. Foot and mouth disease (FMD) is a disease of ungulates that causes severe economic hardship to countries where outbreaks occur or where it has become endemic. In India, Africa, Greece and recently the United Kingdom and Eire, sheep and goats have been implicated in the spread and maintenance of FMD. In Australia, there are contingency plans (AUSVETPLANS) for dealing with an outbreak of FMD. Included in those plans are strategies for control of the disease in feral ungulates including feral pigs and feral goats. Modelling has provided assistance in developing strategies to combat outbreaks in feral pigs and for controlling outbreaks in domestic livestock. No models have been constructed to aid decisions about controlling FMD in feral goats where they co-occur with merino sheep. In Australia, the greatest densities of free-ranging feral goats and domestic livestock occur in the high rainfall zone (> 500 mm mean annual rainfall) along the eastern tablelands and adjacent slopes of the Great Dividing Range. Previous studies of feral goat biology, population dynamics and behaviour in Australia have concentrated on arid and semi-arid zones or on islands. Interactions between free ranging feral goats and merino sheep have not previously been studied in the high rainfall zone. My study investigated the ecological and behavioural characteristics of feral goats and their interactions with sympatric merino sheep at a high rainfall site in central eastern New South Wales. The population dynamics, biological and behavioural parameters of feral goats and sheep were then used to model FMD in such an environment. Deterministic temporal models and a new spatial stochastic model were used. Of particular interest were the rates of contact within and between subgroups of feral goats (termed herds and mobs), within and between subgroups of merino sheep (termed flocks and mobs), and between subgroups of the two species. Feral goats at the study site were found to be numerous (mean density = 34.94 goats km-2, from aerial surveys), in good condition, fecund and had high adult survival and low annual adult mortality (survival= 0.81�1.00) in the absence of harvesting and hunting. They had an observed instantaneous rate of increase of 0.112 per year. Annual rate of increase was similar to other sites in Australia without sustained harvesting pressure. Home ranges were small for both males (3.754 km², s.e. = 0.232, n = 116 goats) and females (2.369 km², s.e. = 0.088, n = 241 goats). From this and other Australasian studies, an inverse power function was found to be an excellent descriptor of the relationship between mean annual rainfall and female home range size. A resource selection function was fitted in a geographic information system to observational data of feral goats. The habitat selection of feral goats included a preference for wooded vegetation on eastern and north eastern aspects at higher elevations. The resource selection function was also used to set the probabilities of occurrence of feral goats in 1 ha areas of the landscape and these probabilities were used to generate heterogeneity in a spatial model of foot and mouth disease virus (FMDV) transmission. Daily per capita contact rates were estimated from observed contacts in the field where a contact between individuals was recognised when one approached within 1 body length ([approx] 1m) of another. The contacts between feral goats within herds were frequent and occurred at a rate of 6.96 (s.e. = 1.27) goat�goat contacts day-1. Sheep to sheep contacts were slightly less frequent (4.22 sheep�sheep contacts day-1, s.e. = 0.65) but both estimates were most likely negatively biased because of observer errors in estimating the number of individual animals coming in contact with observation subject (focal) animals. Contacts between herds of feral goats were not common and those between adjacent populations were fewer than 1 per year. In sheep, flock to flock contact was largely governed by husbandry practices and occurred at a mean daily rate of 0.0014 flock�flock contacts. Contacts between sheep and feral goats were less frequent but nonetheless common (2.82 goat�sheep contacts day-1, s.e. = 0.40). In feral goats the size of the mob in which focal goats were observed was found to be the most important factor in determining contact rates between individuals and a counter-intuitive inverse relationship was identified. Contacts were heterogeneous and density was not an important determinant of contact rates implying that, because of the uniformly high densities at the site, saturation had occurred. The temporal models of FMDV transmission showed that the rate of contact within and between species was such that FMD was predicted to spread rapidly throughout an infected herd or flock. Control strategies of intense culling of feral goats at the population level were predicted to allow the disease to persist at low prevalence, with a small peak corresponding to the annual lambing pulse in sheep. However, the same level of control (>90% reduction) at the herd level was predicted to eliminate FMD and allow the safe reintroduction of sheep. Extreme control that left very small groups (<3 individuals) may be counter productive because such small groups are likely to join the reintroduced sheep in an effort by the goats to meet gregarious urges. The spatial model was more reassuring. It predicted that FMD would die out in a mixed sheep and feral goat population in less than 90 days because of the low rate of herd to herd contact and herd to flock contact. For similar environments, the contingency planning consequences are that an outbreak of FMD introduced into feral goats from sympatric sheep is likely to be containable by removing all the sheep, determining the extent and likely range of the feral goats, then removing a substantial proportion of or eradicating each herd. Feral goats, being relatively sedentary, are unlikely to spread to adjacent populations and the disease will die out through lack of contact between herds and populations. Because feral goat home ranges overlap and are centred on one or two small catchments, a containment ring of feral goat control, set to encompass the home range of a target herd and that of adjacent herds, should be adequate to limit spread of FMD.

This thesis is concerned with studying aspects of the ecology of feral pigs in the wet-dry tropics of the Northern Territory. The data are needed for use in the management of feral pigs to reduce their agricultural and potential epidemiological impact. Particular emphasis is placed on collecting data needed for modelling foot-and-mouth disease in feral pigs, estimating agricultural damage caused by pigs and evaluating control techniques. All fieldwork was conducted in the Douglas Daly district of the Northern Territory.