Background Climate variation has affected diverse physical and biological systems worldwide. Population health is one of the most important impacts of climate variation. Although the impact of climate variation on infectious diseases has been of significant concern recently, the relationship between climate variation and infectious diseases, including vector-borne diseases and enteric infections, needs greater clarification. Australia is grappling with developing politically acceptable responses to global warming. In China, few studies have been conducted to examine the effect of climate variation, including global warming, on population health. As residents of developing countries may suffer more from climate change compared with people living in more developed countries, this thesis has significance for both countries. Aims This study aims to contribute to a better understanding of the impact of climate variation on population health, and to provide scientific evidence for policy makers, researchers, public health practitioners and local communities in the development of public health strategies at an early stage, in order to prevent or reduce future risks associated with ongoing climate change. The objectives of this study include: (1) to quantify the association between climate variation and selected vectorborne diseases and enteric infections in different climatic regions in Australia and China; (2) to project the future burden of selected vector-borne diseases and enteric infections based on climate change scenarios in different climatic regions in Australia and China. Methods This ecological study has two components. The first uses time-series analyses to quantify the relationship between meteorological variables and infectious diseases, whereas the second projects the burden of selected infectious diseases using future climate and population scenarios. Temperate and subtropical climatic zones in both Australia and China were selected as the primary study areas, and a study of an Australian tropical region was also conducted. Study of Australia’s temperate zones was conducted in Adelaide, South Australia, as well as the Murray River region in that State. The study of China’s temperate zone was carried out in Jinan, Shandong Province. Subtropical studies were conducted in Baoan, Guangdong Province, China, and Brisbane in Queensland, whilst research for the tropics centred on Townsville, also in Queensland, Australia. The selected infectious diseases - one vector-borne disease and one enteric infection in each country - are Ross River Virus (RRV) infection and salmonellosis in Australia, and malaria and bacillary dysentery in China. Study periods vary from eight to sixteen years (depending upon the availability of data). Climate data, infectious disease surveillance data and demographic data were collected from local authorities. Data analyses conducted in the ecological studies include Spearman correlation analysis, time-series adjusted Poisson regression and the Seasonal Autoregressive Integrated Moving Average (SARIMA) model with consideration of lag effects, seasonality, long-term trends, and autocorrelation, on a weekly or monthly basis depending on data availability, and Hockey Sticky model to detect potential threshold temperatures. In the burden of disease component, analyses include the calculation of an indicator of the burden of disease - Years Lost due to Disabilities (YLDs) - and use scenario-based models to project YLDs for the selected diseases in 2030 and 2050 in Australia and 2020 and 2050 in China respectively. The projections consider both different scenarios of projected temperature and future population change. Results Relationship between climate variation and selected infectious diseases In all the study regions in Australia, maximum temperature, minimum temperature, rainfall and humidity are all significantly related to the number of RRV infections, with lag effects varying from 0 to 3 months. Additionally, high tides in the two seaside regions with tropical (Townsville) or subtropical (Brisbane) climates, and river flow in the temperate region (Murray River region), are related to the number of cases without any lag effects. A potential 1°C increase in maximum or minimum temperature may cause 4%~23% extra cases of RRV infection in the temperate region, 5~8% in the subtropical region, and 6%~15% in the tropical region. Maximum temperature, minimum temperature, humidity and air pressure are significantly related to malaria cases in the temperate city Jinan and subtropical city Baoan in China, with a lag effect range of 0 to 1 month. An association between rainfall and malaria cases was not detected in either region. A potential 1°C increase in maximum or minimum temperature may lead to 4%~15% extra malaria cases in the temperate region, and 12%-18% in the tropical region in China. Maximum temperature, minimum temperature, rainfall and humidity are all significantly related to the number of salmonellosis cases in the three study cities in Australia, with lag effects varying from 0 to 1 month. A potential 1°C increase in maximum or minimum temperature may cause 6%~19% extra salmonellosis cases in the temperate region (Adelaide), 5%~10% in the subtropical region (Brisbane), and 4%~15% in the tropical region (Townsville). The thresholds for the effects of maximum and minimum temperatures are 20ºC and 12ºC respectively in Adelaide. No threshold temperatures are detected in Townsville and Brisbane. Maximum temperature, minimum temperature, humidity, air pressure and rainfall are significantly related to bacillary dysentery cases in the temperate city Jinan and subtropical city Baoan in China, with the lag effect range of 0 to 2 months. A potential 1°C increase in maximum or minimum temperature may cause 7%~15% extra bacillary dysentery cases in the temperate region and 10% ~ 19% in the subtropical region in China. The thresholds for the effects of maximum and minimum temperatures on bacillary dysentery are 17ºC and 8ºC respectively in Jinan. No threshold temperatures are detected in Baoan. Projection of YLDs from target diseases In Australia, considering both climatic and population scenarios, if other factors remain constant, compared with the YLDs observed in 2000, the YLDs for salmonellosis might increase by up to 48% by 2030, and nearly double by 2050 in South Australia, while the YLDs might double by 2030 and increase by up to 143% by 2050 in Brisbane, Queensland. The YLDs for RRV infection might increase by up to 66% by 2030, and nearly double by 2050 in South Australia. They might increase by up to 61% by 2030 and double by 2050 in Brisbane, Queensland. In China, considering both climatic and population scenarios, if other factors remain constant, compared with the YLDs observed in 2000, the YLDs for bacillary dysentery might double by 2020 and triple by 2050 in both Jinan and Baoan. The YLDs for malaria might increase by up to 108% by 2020 and nearly triple by 2050 in Jinan, the temperate city, and increase by up to 144% by 2020 and nearly triple by 2050 in Baoan, the subtropical city. Conclusions 1. Both maximum and minimum temperatures are important in the transmission of vector-borne diseases in various climatic regions in both Australia and China. River flow or high tides may also play an important role in the transmission of such diseases. 2. Both maximum and minimum temperatures play an important role in the transmission of enteric infections in various climatic regions in both Australia and China, with a threshold temperature detected in the temperate regions but not in subtropical and tropical regions. 3. The effects of rainfall and relative humidity on selected infectious diseases vary in different study areas in Australia and China. 4. The burden of temperature-related infectious diseases may greatly increase in the future if there is no effective preventive intervention. Public health implications 1. Implication for health practice • Public health practitioners, together with relevant government organisations, should monitor trends in infectious diseases, as well as other relevant indexes, such as vectors, pathogens, and water and food safety. They should advise policy makers of the potential risks associated with climate change and develop public health strategies to prevent and reduce the impact of infectious disease associated with such change. • Doctors and other clinical practitioners should be prepared and supported in the provision of health care for any expected extra cases associated with climate variation and should play an important role in relevant health education on climate change. • Community participation is of significance to adapt to and mitigate the risk of climate change on population health. Community involvement helps to deliver programmes which more accurately target local needs. Therefore, community should be involved in the partnerships of climate change as early as possible. • Relevant education programs on the potential health impact of climate change should be conducted by government at all levels for different stakeholders, including industries, governments, communities, clinicians and researchers. • Advocacy for adapting to and mitigating climate change should be a longstanding public health activity. 2. Implication for researchers • The main task for researchers is to identify the independent contribution made by key climatic variables and whether there are exposure thresholds for infectious disease transmission. Further studies should include various infectious diseases in different climatic regions. • Developing countries and rural regions are more vulnerable to the impact of climate change so more research should be conducted for people living in those regions. • Studies using summary measures that combine prevalence of disease, quality of life and life expectancy, such as Disability Adjusted Life Years (DALYs), to assess the burden of disease due to climate change is necessary to assist in decision making. • More research should be conducted on the assessment of adaptive strategies and mitigation to future climate change. 3. Implication for policies • Public and preventive health strategies that consider local climatic conditions and their impact on vector and food borne diseases are important in reducing such impact due to climate change in the future. • The extra health burden that may be caused by future climate change may have a great impact on the currently overloaded public health system in both developed and developing countries. Long-term planning about health resource allocation, infrastructure establishment, and relevant response mechanisms should be developed at relevant government levels. • Effective prevention and intervention strategies will be possible only if the efforts of relevant sectors, including governments, communities, industries, research institutions, clinical professionals and individuals, have coordinated responses. • International and regional collaborations are necessary to address this global issue. In addition, strategies of an international dimension should be translated into regional and local actions. This is extremely important to developing countries such as China and India. • Sustainable development policies with consideration given to reducing green house gases and environmental degradation need immediate action which will benefit future generations. Health priorities should include the prevention of climate change. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1290777 / Thesis(Ph.D.)-- School of Population Health and Clinical Practice, 2007

The Innovative Medicines Initiative Accelerated Development of VAccine beNefit-risk Collaboration in Europe (IMI ADVANCE) project aims to develop a framework for best practice methods on integrated rapid benefit/risk monitoring of vaccines in the European Union (EU). Burden of disease is one of the measures considered when estimating vaccine benefits. This study explores the use of notifiable infectious disease surveillance data for this purpose by estimating burden of invasive meningococcal disease in the EU/European Economic Area (EEA). We use the Burden of Communicable Diseases in Europe toolkit for computing disability-adjusted life years from incidence-based data retrieved from the European Surveillance System (TESSy) held at the European Centre for Disease Prevention and Control. Invasive meningococcal is a common cause of meningitis and septicaemia, with high case-fatality (~10%) and sequelae. We found that the median annual burden of invasive meningococcal disease in the EU/EEA, 2011-2015, was 3.87 DALYs per 100 000 total population (95% UI: 3.79-3.95). Children below one year of age and children below five years of age were at greatest risk of invasive meningococcal disease serogroup B with 89.15 DALYs per 100 000 stratum specific population (95% UI: 83.11-95.02) and 22.57 DALYs per 100 000 stratum specific population (95% UI: 21.03-24.12), respectively. We found that the distribution of burden of invasive meningococcal disease serogroup B differs widely between countries in the EU/EEA and consequently confirm that national assessment of the new infant meningococcal B vaccine is highly relevant.

Philosophiae Doctor - PhD / Injuries, and head injuries in particular, are a common cause of childhood, adolescent and young adulthood morbidity and mortality. The risk factors for injuries in general have been well researched. But it remains uncertain whether these factors are similar for specific injuries, such as head injuries. The inter-relationships between individual and environmental risk factors are difficult to study. Whilst much is know of the short-term consequences of head injuries, relatively little information is available on their long-term conseque~ces. The follow-up period in most research is short (often less than 1 year) and studies are weak in terms of design. Studies generally find a variety of social, cognitive and psychological consequences in children and young adults experiencing head injuries. This study assessed in two large, nationally representative samples, a 1946 birth cohort and a 1997 cross-sectional health survey: 1) the occurrence and risk factors for childhood, adolescent and early adulthood head and other injuries, and 2) the long-term cognitive and psychiatric effects of skull injuries. The overall findings for the risk factors across the two data sets and over 5 decades of data collection were strikingly similar. Maleness was a major risk factor for the head and other injuries. Some of the behaviour and personality factors such as hyperactivity and being neurotic, even after adjusting for sex, socioeconomic status and family type, remained significantly related to injuries, particularly those affecting the head region. A clustering of demographic, socioeconomic, family and behavioural risk factors significantly increased the likelihood of injuries, particularly recurring injuries with at least one being a head injury. In the unadjusted analyses socioeconomic status and family type were less consistently related to injuries. The long-term psychiatric and cognitive consequences of skull injuries causing concussion and skull fractures in childhood and early adulthood were negligible. Other childhood factors such as educational ability, behaviour and personality, and level of education achieved were more predictive of psychiatric symptoms and cognitive problems in adulthood. This study suggests that children and adolescents with behavioural and personality problems were at greater risk of head and other injuries in childhood, adolescence and later in adulthood. Children and adolescents with behavioural and personality problems were more likely to live in manual social class families and families with a single parent or stepparent. This combination of behavioural problems and deprived socioeconomic and family circumstances may increase tendencies for violent behaviour, alcohol dependence and manual occupations later in adulthood, which all increase the risk of injuries. There is therefore a need to identify children and adolescents with behavioural and personality problems as early as possible to prevent the impact in the short- and longterm. This will not only reduce the burden of injuries but also the many other consequence of behavioural and personality problems, particularly when located within deprived socioeconomic and family circumstances.

「被忽視」的熱帶疾病(NTDs)中的寄生蟲疾病(Parasitic Diseases; PDs)除對非洲人群健康之危害甚鉅外，並進而對非洲地區社經體系造成嚴重衝擊與造成巨大的「失能調整人年」損失。由於不易取得治療PDs傳統基本藥物的問題，許多非洲民眾便以其部落社區的傳統治療師所採用的傳統草藥來進行PDs的治療，雖然這些傳統草藥容易取得，但是成分的內容和藥效品質甚或產生嚴重的致命副作用。雖然TRIPS協定第31條和杜哈宣言的第五和第六段對於製藥能力不足或大部分皆無製藥能力的貧窮國家，可以基於「國家緊急危難或其它緊急狀況」的事由，以強制授權方式取得專利藥或較便宜的學名藥以解決造成國家危難的特定公共健康事件，但是國際大藥廠認為無利可圖，不願意花費資金投注於預防或治療此類疾病藥物的相關研發外，高收入的國家為保護其大藥廠的藥物專利，也往往使用一些經濟制裁手段逼迫上述國家就制定國內專利法以保護其藥物專利。雖然經杜哈宣言修正TRIPS協定第31(f)條有關強制授權對外出口的障礙，但是出口國對於強制授權程序與是否能取得政治上和藥廠業者的支持，仍充滿困難。應用「專利池」可以減少交易成本或法律爭議而可調和「強制授權」與解決「權利耗盡」的爭議，有助於解決非洲開發中國家取得專利藥物的困境。PDs造成非洲開發中國家民眾失能等長期痛苦與健康生活損失，類推適用SARS模式，可依TRIPS協定第31條(b)與杜哈宣言第五段(c)將之視為「造成國家緊急危難或其它緊急狀況」的重大公共健康的事由而可行使強制授權。雖然「生醫專利池BVGH」的「非獨家個別授權與免授權費」的操作模式與傳統電信技術專利池不盡相同，但因藥廠不願投入治療PDs的傳統基本藥物存在的副作用與抗藥性的新藥研發，為鼓勵對治療PDs的藥物進行創新研發， BVGH彈性的授權方式與免繳交授權費，將有利於解決開發中國家未來取得新專利藥的困境。除BVGH外，建議結合全球獎勵基金以「激勵拉拔」的方式獎助願意投入治療PDs新藥研發並將專利自願授權給BVGH的藥廠。鑒於全球暖化與最近中東難民潮大量湧進歐洲，罕見的PDs可預期會大量傳播開來，將嚴重衝擊歐洲等先進國家良好的公共衛生體系，而使得「NTDs尤其是PDs不再只是專屬於貧窮國家的疾病，亦將常現於富有的先進國家」。這些NTDs疾病將提供藥廠進行新藥研發的利基，然而在未來可能產生專利池的反競爭問題，導致支配市場獨占性的隱憂值得關注。 / Parasitic diseases (PDs) not only cause the huge health hazards to African populations, but also they further severely impact on African socio-economic system as resulting in huge economic and health losses as assessed by disability adjusted life-years. Since it is not easy for Africans to access the essential medicine to treat PDs, many of them will seek for the help of local healers in tribal communities to treat PDs. Although these traditional herbs are readily available, the content and quality of drug ingredients may even cause serious fatal side effects. Poor countries with insufficiencies or lacks of the pharmaceutical capacities may still access the patented medicines or cheaper generics to solve the national crisis caused by the specific public health events through compulsory licensing (CL) based on "national emergency or the other emergency situations" according to TRIPS Article 31 and Doha Declaration on the fifth and sixth paragraph due to that the large international pharmaceutical companies consider unprofitable, unwilling to spend money to invest on the research and development (R&D) of new drugs for prevention or treatment purpose. Moreover, the high-income countries also tend to exert some of the economic sanctions to force those poor countries to enact national patent law in order to protect drug patents. Furthermore, the mandatory obstacle of exportation authorized by CL from the amended TRIPS Agreement Article 31 (f) by the Doha Declaration has been improved; nevertheless, it is still fraught with difficulties in utilization of CL for the exporting countries because this should be dependent on whether they may actually get the supports from political and the pharmaceutical industry. Application of patent pools model may benefit to reduce transaction costs or legal dispute thus reconciling and resolving issues related to CL as well as doctrine of patent exhaustion and that it is beneficial to help solve dilemma for African countries to access patented drugs. Because Africans severely suffer from disabled caused by PDs thus leading to long-term pain and health life losses, African countries can grant CL as PDs may be regarded as national crisis like SARS causing "national emergency or the other emergency situations" as authorized from TRIPS Agreement Article 31 (f) and Doha Declaration paragraph 5 (c). Although the practice of individual licensing with royalty-free for BVGH is somewhat different from that of traditional patent pools, this licensing practice mode is beneficial to innovation in new drugs R&D to improve the side effects and drug-resistance of traditional essential medicines and help African countries to access patented new drugs in the future. Finally, it is recommended to cooperate with Award Foundation to encourage incentive for pharmaceutical companies which contribute most to new drugs R&D and voluntary licensing to BVGH. Owing to global warming and recent emergence of huge refugees into Europe rare PDs will be obviously spread out thus causing severe impacts on well-established public health system as leading to emergence of PDs in developed countries like Europe. Altogether, such situations definitely provide a good incentive in new drugs R&D for pharmaceutical companies; however, it guarantees concerns on anti-competitive and monopoly issues derived by biomedical pools in the future.

Cette thèse étudie théoriquement et empiriquement les interrelations entre la santé de la population, la dégradation de l'environnement et le développement économique, ses conséquences pour les pays en développement, et fournit certaines réponses en termes de politique économique. Elle est subdivisée en deux parties. La première partie s’intéresse à la relation entre l’environnement, la santé, et les inégalités. Elle analyse dans un premier temps l’hypothèse selon laquelle la dégradation de l'environnement pourrait être considérée comme un canal supplémentaire par lequel les inégalités de revenu affectent les taux de mortalité infantile et juvénile (chapitre 2). Nos travaux théoriques et empiriques montrent que les inégalités de revenu affectent négativement la qualité de l'air et de l'eau, et cela à son tour dégrade la santé de la population. Par conséquent, la dégradation de l'environnement peut être considérée comme un canal non négligeable à travers lequel les inégalités de revenu influence l’état de santé. Il est ensuite démontré que les émissions de dioxyde de soufre (SO2) et celles des micro-Particules (PM10) sont en partie responsables des grandes disparités dans la mortalité infantile et juvénile au sein des pays pauvres (chapitre 3) .En outre, nos résultats soutiennent l’idée selon laquelle les institutions démocratiques jouent un rôle de protection sociale en atténuant cet effet pour les classes de revenu les plus pauvres et ainsi réduisent les inégalités de santé provoquées par la pollution. La deuxième partie évalue le lien entre la santé, l'environnement et la croissance économique. Le Chapitre 4 évalue l'effet de la santé (charge globale de la maladie, maladies transmissibles et paludisme) sur la croissance économique. Ce chapitre montre que les indicateurs de santé, lorsqu'ils sont correctement mesurés par l'écart entre l'état de santé actuel et une situation de santé idéal où toute la population vit à un âge avancé, indemne de maladie et d'invalidité, et lorsqu’ils sont convenablement instrumentés, ont un impact négatif significatif sur la performance économique. Les conséquences de ces interactions sur la convergence économique des pays pauvres vers leur état régulier, sont théoriquement et empiriquement analysées dans le dernier chapitre. Il en ressort que la dégradation de l'environnement réduit la capacité des pays pauvres d'atteindre leur état régulier, renforçant ainsi notre argument théorique selon lequel l’amélioration de la qualité de l'environnement joue un rôle considérable dans le processus de convergence économique. En outre, la dégradation de la qualité de l'air et de l'eau affecte négativement la performance économique, et l'état de santé demeure un canal important par lequel la dégradation de l'environnement agit sur la croissance économique même si elle n'est pas le seul. L’hypothèse de la courbe environnementale de Kuznets (EKC) est également vérifiée. / This dissertation investigates theoretically and empirically the interrelationships among population’s health,environmental degradation and economic development, its consequences for developing countries, and someeffective policy responses. The first part explores the association between health, environment, and inequalities. Itfirstly analyzes whether environmental degradation could be considered as an additional channel through whichincome inequality affects infant and child mortality (chapter 2). Theoretical and empirical investigations show thatincome inequality affects negatively air and water quality, and this in turn worsens population’s health. Therefore,environmental degradation is an important channel through which income inequality affects population health. Then,it is shown that sulphur dioxide emission (SO2) and particulate matter (PM10) are in part responsible for the largedisparities in infant and child mortalities between and within developing countries (chapter 3). In addition, we foundthat democratic institutions play the role of social protection by mitigating this effect for the poorest income classesand reducing the health inequality it provokes. The second part is devoted to the link among health, environment,and economic growth. The effect of health (global burden of disease, communicable disease, and malaria) oneconomic growth is assessed in Chapter 4. This chapter shows that health indicators, when correctly measured by thegap between current health status and an ideal health situation where the entire population lives to an advanced age,free of disease and disability, and when accurately instrumented have significant impact on economic performance.The consequences of these interrelationships on the convergence of poor countries towards their steady state aretheoretically and empirically investigated in the last Chapter (chapter 5). It is found that environment degradationreduces the ability of poor countries to reach their own steady state, reinforcing our argument according to whichenvironment quality improvement plays a considerable role in economic convergence process. Moreover, thedegradation of air and water quality affects negatively economic performance, and health status remains an importantchannel through which environment degradation affects economic growth even if it is not alone. The EnvironmentalKuznets Curve (EKC) hypothesis is also verified.