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# Emerging infectious diseases in Asia

Authored by: Peter Horby

# Routledge Handbook of Global Public Health in Asia

Print publication date:  April  2014
Online publication date:  April  2014

Print ISBN: 9780415643825
eBook ISBN: 9781315818719

10.4324/9781315818719.ch18

#### Abstract

The former US Surgeon General William H. Stewart is often quoted as having said, in the 1960s, ‘It is time to close the book on infectious diseases and declare the war against pestilence won.’ Although it seems he was misquoted and never actually said this, it is true that the 1960s was a period of optimism for the health sector, when the power of sanitation, antibiotics, vaccination and vector control seemed to herald an end to infectious diseases [1, 2]. This optimism, however, was dashed when HIV emerged and the term ‘emerging infectious disease’ (EID) rose in popularity throughout the 1980s. The use of the term reached a high in 1992 following the publication of the US Institute of Medicine report, ‘Emerging Infections: Microbial Threats to Health in the United States’. The journal Emerging Infectious Diseases was subsequently launched in 1995 and the National Library of Medicine added the medical sub-heading ‘Communicable Diseases, Emerging’ to PubMed in 2001.

#### Introduction

The former US Surgeon General William H. Stewart is often quoted as having said, in the 1960s, ‘It is time to close the book on infectious diseases and declare the war against pestilence won.’ Although it seems he was misquoted and never actually said this, it is true that the 1960s was a period of optimism for the health sector, when the power of sanitation, antibiotics, vaccination and vector control seemed to herald an end to infectious diseases [1, 2]. This optimism, however, was dashed when HIV emerged and the term ‘emerging infectious disease’ (EID) rose in popularity throughout the 1980s. The use of the term reached a high in 1992 following the publication of the US Institute of Medicine report, ‘Emerging Infections: Microbial Threats to Health in the United States’. The journal Emerging Infectious Diseases was subsequently launched in 1995 and the National Library of Medicine added the medical sub-heading ‘Communicable Diseases, Emerging’ to PubMed in 2001.

Emerging infectious diseases are often thought of as ‘novel’ (newly recognized) pathogens of humans, but are actually defined as diseases that are increasing in their incidence, geographic or host species range or their impact (due, for instance, to the acquisition of resistance to antimicrobial drugs or vaccines or the acquisition of new virulence factors). The definition therefore encompasses both newly recognized pathogens and known pathogens that are ‘re-emerging’. The development and introduction over time of new, more sensitive technologies for identifying microbial diversity, such as molecular methods to identify elements of the microbial genome, coupled with geographical heterogeneities in the availability of these technologies, make it difficult to accurately assess where and when new infectious diseases first emerge. The difficulty is further compounded by changes over time in the ease of publishing articles in bio-medical literature. Attempts have nevertheless been made and 335 emerging infectious disease events were identified between 1940 and 2004, an average of five per year, with a peak in the 1980s relating to the emergence of HIV/AIDs and its associated opportunistic infections [3].

#### Asia as a ‘hotspot’ for emerging infectious diseases

One analysis has identified Asia as a ‘hotspot’ for EIDs and indeed some of the most high profile EIDs in the last decade, such as SARS and highly pathogenic avian influenza H5N1, arose in Asia. Conversely, however, equally notorious EIDs such as HIV, bovine spongiform encephalopathy (BSE or mad-cow disease) and pandemic influenza H1N1 (swine flu) arose outside Asia. The premise that Asia is a hotspot for EIDs is based on the distribution of 335 EIDs after correcting for spatial differences in disease reporting and the distribution of some putative ‘drivers’ of EID events (population density, population growth, latitude, rainfall and richness of wildlife host species) [3]. This assessment of Asia as a hotspot for EIDs must be balanced against the fact that only 17 per cent (56/335) of EID events identified were detected in Asia.

Table 18.1 shows 59 EID events that were first identified in Asia from 1940 to 2011 (56 were identified by Jones et al. and three additional ones are more recent events). This table shows that the emergence of a previously unrecognized human pathogen that results in a significant number of human infections is rare. Since their identification, SARS and H5N1 have together resulted in fewer than 1,400 deaths globally, 1,000 times fewer than the estimated 1.4 million childhood deaths from pneumonia every year [4]. The potential for SARS and H5N1 to evolve into devastating epidemics does however necessitate that they are taken seriously and the fear of this ‘potential’ has resulted in economic consequences that far outweigh the actual, realized health impacts. The economic consequences of SARS, for example, have been estimated at US$3–10 million per case [5]. ### Table 18.1 Emerging infectious diseases (EID) identified in Asia, 1940–2011 Pathogen Year Pathogen type Driver Location Acinetobacter baumannii multi-drug-resistant 1998 Bacteria Antimicrobial agent use Taiwan Angiostrongylus cantonensis 1945 Protozoa International travel and Taiwan Banna 1985 Virus Medical industry changes China Burkholderia pseudomallei 1965 Bacteria War and famine Vietnam Chlamydia pneumonaie TWAR strain 1965 Bacteria Unspecified Taiwan Dengue 1954 Virus War and famine Philippines Ehrlicia sennetsu 1953 Rickettsia International travel and commerce Japan Escherichia coli O118:H2 1996 Bacteria Food industry changes Japan Escherichia coli O145:H5 1990 Bacteria Food industry changes Japan Far Eastern tick borne encephalitis 1993 Virus Land use changes Japan Haemophilus influenzae amp/cm/tmp-smz-res 1979 Bacteria Antimicrobial agent use Thailand Haemophilus influenzae chlor/amp-res 1979 Bacteria Antimicrobial agent use Thailand Hantaan 1941 Virus Land use changes China Hepatitis E 1955 Virus Unspecified India Human T-lymphotropic virus 1 1974 Virus Human susceptibility to infection Japan Influenza A (H5N1) 1997 Virus Agricultural industry changes China (Hong Kong) Klebsiella pneumoniae 1981 Bacteria Human susceptibility to infection Taiwan Kyasanur forest disease virus 1957 Virus Land use changes India Leptospira interrogans 1950 Bacteria War and famine Malaysia Leptospira weilii 2000 Bacteria Land use changes Malaysia Mycobacterium shimoidei 1975 Bacteria Human susceptibility to infection Japan Mycobacterium tuberculosis isoniazid-res 1981 Bacteria War and famine North Korea, South Korea Neisseria gonorrhoeae pen/tet/cipr-res 1996 Bacteria Antimicrobial agent use Japan Neisseria meningitidis serogroup 1966 Bacteria International travel and China A termed subgroup III commerce New Delhi metallo-beta-lactamase1 (NDM-1) 2009 Bacteria Antimicrobial agent use India Nipah virus 1998 Virus Agricultural industry changes Malaysia Nosema connori 1973 Protozoa Human susceptibility to infection Japan Plasmodium falciparum artemisinin-res 2009 Protozoa Antimicrobial agent use Cambodia Plasmodium falciparum mefloquine-res 1982 Protozoa Antimicrobial agent use Thailand Plasmodium falciparum multiple drug-res 1991 Protozoa Land use changes Thailand Plasmodium falciparum proguanil-res 1948 Protozoa Antimicrobial agent use Malaysia Plasmodium falciparum quinine-res 1960 Protozoa Antimicrobial agent use Thailand Plasmodium falciparum sulfadoxine-primethamine-res 1981 Protozoa Antimicrobial agent use Thailand Plasmodium vivax 1964 Protozoa Breakdown of public health measures India Plasmodium vivax proguanil-res 1948 Protozoa Antimicrobial agent use Malaysia Poliovirus type 2 2003 Virus Human demographics and behaviour India Pseudomonas aeruginosa imipenem-res 1988 Bacteria Antimicrobial agent use Japan Rickettsia honei 1990 Rickettsia International travel and commerce Thailand Rickettsia japonica 1984 Rickettsia Unspecified Japan Salmonella enterica serovar typhi 3rd generation cephalosporin-res 1999 Bacteria Agricultural industry changes Bangladesh Salmonella enterica serovar typhi cipro-res 1991 Bacteria Antimicrobial agent use Nepal Salmonella enterica serovar typhi CT-18 1993 Bacteria Antimicrobial agent use Vietnam Salmonella enterica serovar typhi multi drug-res 1990 Bacteria Antimicrobial agent use Pakistan Salmonella paratyphi multidrug-res 1997 Bacteria Antimicrobial agent use Pakistan SARS coronavirus 2002 Virus Bushmeat China Schistosoma japonicum 1950 Helminth War and famine China Serratia marcescens fluoroquinolone-res 1986 Bacteria Antimicrobial agent use Taiwan Shigella dysenteriae 1998 Bacteria Breakdown of public health measures Indonesia Shigella dysenteriae multidrug-res 1955 Bacteria Antimicrobial agent use China Shigella dysenteriae sulfa-res 1949 Bacteria Antimicrobial agent use Japan Shigella dysenteriae tet-res 1953 Bacteria Antimicrobial agent use Japan Staphylococcus haemolyticus multidrug-res 1997 Bacteria Antimicrobial agent use India Streptococcus suis serotype 2 2005 Bacteria Agricultural industry changes China Strongyloides stercoralis 1949 Helminth War and famine Vietnam Vibrio cholera O1 El Tor 1961 Bacteria Breakdown of public health measures Indonesia Vibrio cholera O139 1992 Bacteria International travel and commerce India Vibrio fluvialis 1965 Bacteria Climate and weather Bangladesh Vibrio parahaemolyticus 1950 Bacteria Climate and weather Japan Zika virus 1977 Virus Climate and weather Indonesia Over 60 per cent of the world’s population lives in Asia and the region is home to some of the fastest developing economies in the world. Yet despite tremendous advances, infectious diseases still remain a major burden in Asia. Of the estimated 2.1 million deaths in children aged less than 5 years in Southeast Asia in 2010, 47 per cent were attributed to infectious causes [4]. As such, Asia is both vulnerable to imported EIDs and is a powerhouse of social and environmental change that may facilitate the emergence of new pathogens. However, it would be simplistic and disingenuous to present the extensive changes in Asia as inevitably increasing the risk of EIDs. Many of the socio-economic changes, such as urbanization; industrialization and commercialization of agriculture and food production; increased international connectivity; and globalization of information and trade, may reduce the risk of disease emergence. #### Causes of emergence: conditions and events The world is laden with microbes. They are the second most abundant life form on earth (after plants) and they are essential to our survival: fixing nitrogen, degrading organic materials, and ensuring the functioning and integrity of the gut, genital tract, and immune system of animals [6]. Each of us hosts many more microbial cells than we have cells of our own (99 per cent of all cells in a human body are microbial) but this symbiotic relationship hides a ‘universal struggle for life’, with each species trying to blindly optimize its own survival [7]. Our relationship with microbes is therefore interdependent and whilst most of them are beneficial or harmless, occasionally they are harmful and are responsible for causing diseases. Ecological factors (specifically the environmental living conditions) rather than genetic or geographic constraints seem to critically define pathogen niches, and whilst the conditions or events that result in the emergence of new human pathogens are not well understood, they are often precipitated by changes to ecological or biological systems that result in pathogen dispersal or pathogen adaptation (through natural selection). The most successful EIDs are characterized by a process of both dispersal and adaptation [8]. The events leading to dispersal or adaptation can take many forms and occur on many scales, such as altered patterns of domestic and wild animal contact (e.g. Nipah virus) or human and animal contact (e.g. HIV, SARS), drug pressure (e.g. artemisinin resistant malaria) and changes in species diversity (e.g. Lyme disease). Species diversity, including the diversity of pathogenic microbes, increases closer to the equator [9] and a correlation between the emergence of zoonotic pathogens and the diversity of mammalian wildlife species has been reported [3]. Indeed, around 60 per cent of emerging infections identified since 1940 have arisen from animals and primarily from wild animals [3, 10]. Whilst wild animal and pathogen species diversity may be associated with an increased burden of infectious diseases and a consequent risk of disease emergence, a reduction of species diversity may, perhaps counterintuitively, be associated with increased disease transmission. Species diversity loss directly disrupts the functioning and stability of ecosystems, producing effects that can extend well beyond the particular species lost [11]. As such, a variety of mechanisms may favour pathogen dispersal, including reduced predation and competition resulting in increased abundance of competent hosts, and the loss of ‘buffering species’ leading to increased contact between amplifying host species and pathogens [12]. Tropical regions with a rich pool of existing and potential pathogens that are increasingly connected, but that are also experiencing high rates of ecosystem disruption and biodiversity loss, may therefore be at a particularly high risk of disease emergence. Even though new human pathogens occasionally emerge as a result of dynamics that apparently do not involve humans, for example the emergence of Vibrio cholera O139 and Cryptococcus gattii, most ecological disturbances resulting in an EID seem to originate in the actions of humans. A wide range of factors have been linked to infectious disease emergence, including changes in land use, travel, trade, demographics and climate, but nearly all of these associations are speculative, with little hard data [13]. This is because ecological and biological systems are highly complex and multilayered, and predicting the impact of particular conditions or events on the functioning of a system is difficult, with further inference of the impact of any changes on the risk of pathogen emergence posing a formidable challenge. There are a handful of well-researched case studies where the ecosystem disruption that has resulted in increased disease risk to humans has been identified, for example, the emergence of Lyme disease in the United States and the Nipah virus in Malaysia, but general principles or rules are hard to identify from these specific examples. #### Economic development and altered ecosystems Over the past two decades, Asia has been home to many of the top performing world economies and this macroeconomic success has resulted in large increases in demand for natural resources. The demand for hardwood, firewood, pulp, agricultural and grazing land, living space, roads, minerals and power has had an enormous impact on the landscapes of Asia. Deforestation occurred throughout the 1990s and the area of primary forest in Asia has continued to decline, with net forest loss continuing in Myanmar, Cambodia, Indonesia and Papua New Guinea. However, the last decade has seen net increases in the overall forested areas of Asia due to active afforestation (which includes commercial plantations) in China, India, the Philippines and Vietnam [14]. Deforestation, forest fragmentation and afforestation are all, however, alterations in habitat, which changes species composition and the interaction between wild animals, domestic animals, insect vectors and humans, thereby providing new opportunities for disease emergence. There are well-documented examples of deforestation and forest encroachment resulting in increases in infectious diseases, such as the Oropouche virus, Chagas disease and Hantaan virus [15]. Across much of Asia, however, there are already very high pressures on productive land and the peak in land-use change in Asia has probably passed, with much of the continent now in an era of increasing intensification of land productivity. This intensification is driven largely by demographic pressures, which are predicted to result in a 70 per cent increase in food production by 2050, with decreased consumption of grains and increased demand for meats, fruits and vegetables [16]. The increased demand for food (and meat in particular), when combined with demands for natural resources from industry and domestic consumers and river damming for hydroelectric power, is increasing the stress on water resources [16]. The consequences of intensi-fied agricultural production include the depletion and degradation of river and groundwater, reduced soil quality and biodiversity loss. A direct and predictable effect of reduced access to clean water for low-income families is an increased risk of water-washed diseases such as trachoma and scabies, and water-borne diseases such as typhoid, cholera, and hepatitis A and E. However, unquantified risks arising from the intensification of agriculture include fresh water pollution with pesticides and fertilizers, loss of biodiversity and land abandonment by small-scale farmers. The potential consequences of these changes on the risk of infectious disease emergence have not yet been assessed. #### Livestock production Demand for livestock products in Asia has risen dramatically over the last 50 years, with the per capita consumption of meat in developing countries more than tripling since the early 1960s and egg consumption increasing five-fold [17]. The increased demand for animal products has been met by more intensive and geographically concentrated production of livestock, especially pigs and poultry. Much of this has been through expansion of small-scale production units but industrial-style commercial premises are also increasing. High-density monoculture of domestic animals is a form of low biodiversity that poses a particular threat to the spread of infectious diseases from wild animal reservoirs to humans. Genetic diversity within an individual host species is important since genetic diversity limits the potential for devastating epidemics [18]. The Nipah virus outbreak in Malaysia and Singapore in 1998–1999 is a good example. Once the Nipah virus crossed from wild bats to domesticated pigs, an explosive outbreak in high-density pig farms resulted in widespread exposure of humans and over 250 human cases of encephalitis [19]. Highly pathogenic avian influenza H5N1 is another example, where crossover from wild aquatic birds (the normal reservoirs of influenza A viruses) to humans arose via massive amplification in domestic poultry. However, the intensification of livestock farming often entails improvements in the separation of domestic and wild animals, improved veterinary supervision and input, reduced movement and species mixing. Reducing contact between domestic and wild animals, whether the wild animals are wild or captive in markets, is a key tactic of the Food and Agriculture Organization (FAO) to decrease the risk to human health and is part of the wider FAO strategy of ‘biosecurity’. The reduction of risk in live animal markets (wet-markets) involves the separation of species, not allowing animals to remain in the market for more than 24 hours, not allowing live animals to exit the market, improved cleaning and disinfection, and weekly rest-days, when all animals are removed and the market is thoroughly cleaned. Improving biosecurity in farms is a major challenge since a large proportion of farming in Asia is small-scale backyard production, and there is often a mix of commercial and backyard farming in any one location. Achieving improvements in biosecurity without adversely affecting the livelihoods of small-scale farmers requires an approach to risk management that is ‘As Low As Reasonably Achievable’. The longer-term vision is to restructure the livestock production sector towards a more commercialized and controlled system, which benefits animal health, human health and commercial profitability. Increasing intensification of animal husbandr y in Asia may be a trade-off between a lower risk of emergence events, as animals are ‘healthier’ and better isolated, but should an EID even occur, there may be a greater risk of massive amplification in large, naive monocultures. Perhaps the greatest risk arises when there is a mixed economy with substantial backyard farming with little or no biosecurity, linked through extensive and poorly regulated market chains to large international commercial organizations. This is the situation throughout much of Asia and, as such, the risk of the dispersal and adaptation of zoonotic infections via domestic animals remains substantial. Wild animal products are popular in Asia and are used in traditional medicines, tonics and delicacies, or appear as symbols of wealth. Although all ten countries in the Association of Southeast Asian Nations (ASEAN) are signatories to the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES), Asia continues to host the largest illegal wildlife trade in the world [20]. The capture and use of wild animals for food (bush-meat) has been implicated in the emergence of HIV and SARS, although the animal species that transmitted SARS to humans, the civet cat, is not the reservoir species for SAR-coronavirus (the reservoir is bats) [21]. Growing wealth has increased the demand for wild animal products, and whilst the development and enforcement of regulations on the capture and trading of wild animals has improved, regulation is a weak tool in the face of intense consumer demand. Many large cities in Asia have begun to ban, or more tightly regulate, live animal markets in the wake of SARS and H5N1, but complex and poorly regulated food manufacturing and distribution chains still offer ample opportunities for disease outbreaks. A critical challenge in the control of foodborne outbreaks is the traceability of foodstuffs, particularly fresh meat and vegetables. Food safety is, however, high on the agenda of many Asian countries following a number of high-profile food contamination scandals, such as the adulteration of formula milk with melamine in China. Rudolf Virchow was one of the earliest proponents of a concept that is now known as ‘One Health’, which states that ‘between animal and human medicine there are no dividing lines — nor should there be’. ‘One Health’ has gained popularity recently as a concept to stimulate cross-sectoral solutions to animal and human health problems. Whilst this has had some success at higher levels of decision-making, the real difficulty remains at the local, implementing level, where the day-to-day activities of animal health workers and human health workers rarely intersect. Antibiotics are used extensively in the livestock and aquaculture sector in Asia to treat or prevent infections, or as growth promoters. Non-therapeutic use of antibiotics as growth promoters involves the prolonged administration of sub-therapeutic doses. This practice has a demonstrable effect on the emergence and prevalence of resistant microorganisms in food, animals and their environment, as well as resulting in the excretion of antibiotics into the environment where environmental bacteria may be subject to antibiotic selection pressures [22]. While there remains some debate about the overall impact of these factors on human health, it is clear that the continued use of non-therapeutic antibiotics in an agriculture industry that is rapidly increasing in scale and intensity, poses a very real threat. #### Travel and trade Cities are mixing vessels and hubs of connectivity, and can play a central role in the amplification and dissemination of EIDs. SARS is a classic example of the role of contemporary cities in the emergence of an EID. The initial international dissemination of SARS was via a hotel in Hong Kong where international travellers crossed paths, and it was then further amplified and dispersed through large urban hospitals. Global connectivity continues to increase, with only 10 per cent of the world now classified as remote (more than 48 hours travel time to a big city) and 95 per cent of the world’s population living on just 10 per cent of the land. The development of a regional road transport network within East and Southeast Asia may be especially important since, compared to air travel, roads offer a more egalitarian form of connectivity that includes animals and goods as well as humans. Whilst this provides opportunities for pathogens to disperse beyond their traditional niche [23], it may also benefit mankind by ensuring that no populations are completely unexposed to a pathogen species, thereby avoiding the devastating epidemics that often followed the first contact with isolated populations in the past [24]. #### Human demographics and behaviour Between 2011 and 2050, the world’s population is expected to increase by 2.3 billion (a 32 per cent increase) and over the same period, the global urban population is expected to rise from 3.6 billion to 6.3 billion (a 72 per cent increase). Therefore, all of the population increase in the next 40 years will be concentrated in cities [25]. Most of this growth will occur in developing countries, particularly Asia, which will experience an increase in its urban population of 1.4 billion people. Whilst mega-cities (cities with a population of at least 10 million) receive a lot of attention, most urban dwellers live in small cities, with half of the global urban population in 2011 living in cities of less than 500,000 people. In many ways, this is a good thing and the popularity of cities is a testament to the fact that cities generally offer better economic opportunities, better education opportunities, better living conditions, better nutrition, better sanitation and, therefore, better health, than underdeveloped rural areas. However, given the scale of urbanization, urban humanitarian crises, including epidemic diseases, are a particular concern for the future [26]. Cities are important in the epidemiology of many infectious diseases as they may act as ‘pacemakers’ of local epidemiology (e.g. dengue), become hubs for national and global spread (e.g. SARS and HIV) or act as a bridge between human and animal ecosystems (e.g. H5N1). Increasing travel and medical tourism in Asia adds a new dimension, with the potential for the generation and dissemination of healthcare associated infections, such as the bacterial enzyme New Delhi metallo-beta-lactamase-1 (NDM-1) that confers resistance to a range of potent antibiotics, the carbapenems. Urbanization and urban infrastructures have played an important role in Asia’s success in improving access to safe water and sanitation, with almost half of the world’s population, living in China and India, gaining access to improved sources of drinking water between 1990 and 2008. However, the rate of increase in access to improved drinking water sources is barely keeping up with the rate of urban population growth. With large growths anticipated in urban populations in Asia and water scarcity predicted by the United Nations (UN) to be a major challenge of the twenty-first century, there is a risk that the pace of urban population growth will outstrip the delivery of a healthy infrastructure. Although better on average, cities are also home to great inequalities and the health of the urban poor can be as bad as, or even worse than, that of the rural poor. Whilst China and India have together taken 125 million people out of slum conditions between 2000 and 2010, urban slums remain a concern, with an estimated 500 mil lion people living in slums in Asia in 2010 [27]. In China, at the end of 2008, the number of rural migrant workers was estimated at around 140 million [28]. Circular and temporary migration between rural and urban settings may allow the introduction of pathogens from wild or rural ecosystems and amplification in settings with high concentrations of migrant workers. The tropical urban environment suits certain vector species, particularly Aedes aeypti and Aedes albopictus mosquitoes, which breed in water containers of urban households. Increasing urbanization is one factor that has contributed to the inexorable spread of dengue in the last 50 years and of chikungunya since 2000, such that these are now major public health problems in large parts of tropical and subtropical Asia [29]. Vector control in tropical urban settings is a major challenge, as demonstrated by the experience of one of the richest and most developed cities in Asia, Singapore, which spends an estimated US$4,500 per Disability Adjusted Life-Year averted and yet has failed to eliminate dengue transmission [30]. Whilst vector control is not currently a cost-effective solution for most countries in Asia, the development of genetically modified sterile male mosquitoes, and of mosquitoes infected with the intracellular bacterium Wolbachia (which limits the susceptibility of the mosquito to dengue), perhaps offer new hopes for vector control.

In addition to changes in the physical living environment, urbanization is accompanied by many different lifestyles changes. Urbanization often results in an expansion of social and sexual behaviours, which may offer new opportunities for diseases transmitted by social or sexual contact. The apparent emergence of enterovirus 71 (one of the viruses causing hand, foot and mouth disease) in Asia over the past decade may be in part attributable to changes in childcare practices and the increasing concentration of young children in pre-school environments.

#### Health systems

Almost 40 per cent (23/59) of EIDs identified in Asia since 1940 represent the emergence of a new pattern of antimicrobial resistance (see Table 18.1). The most important driver of antimicrobial resistance is drug pressure. The sequential development of resistance by malaria parasites in Asia to chloroquine, sulphadoxine-pyrimethamine, mefloquine and, now, artem-isinin is a measure of both the adaptive capacity of the parasite and the failure of health systems to implement effective drug combination and cycling strategies to avoid resistance. Bacteria in Asia show alarmingly high rates of resistance to anti-bacterial agents, including multi-drug resistant Acinetobacter baumanii, Salmonella enterica, Enterobacteriaceae and tuberculosis. The recent emergence of the NDM-1 resistance gene in Asia and its rapid dissemination to other regions highlights the serious threat of antimicrobial resistance. The growth of multi-drug resistant (MDR) and extensively drug-r esistant (XDR) tuberculosis in Asia is also alarming, with China’s rates of MDR TB in 2007 being twice the global average. Although drug resistance initially develops as a consequence of inadequate treatment, the majority of detected MDR and XDR TB cases in China are now the result of primary acquisition of resistant strains, without prior treatment [31].

Whilst malaria remains a serious problem in Asia (with an estimated 658 million people in Central, South and East Asia living in areas with stable Plasmodium falciparum transmission and 876 million people living in areas with stable P. vivax transmission in 2010), improved living conditions, vector control, rapid case identification and treatment, and insecticide impregnated bed nets have resulted in a substantial decline in the burden of malaria in Asia and a contraction of the areas where malaria transmission is stable [32, 33]. However the threat of artemisinin resistance, now detected in western Cambodia and western Thailand, is substantial and, together with insecticide resistance, threatens to reverse some of these health gains.

A high level of antimicrobial resistance is a marker of a failure of health systems to control access to antibiotics and to influence prescribing behaviours. Antibiotics are easily available over the counter from pharmacists and drug-sellers without a prescription throughout much of Asia, including in Pakistan, India, Bangladesh, China, Vietnam, Thailand and Indonesia, even though antibiotics are officially prescription-only medicines in most of these countries. A vast number of people are therefore receiving unnecessary or inappropriate antibiotics, creating a massive pressure for the development of resistance. There is also unnecessary and inappropriate prescription of antibiotics within the primary and secondary healthcare systems, which is a particular issue for tuberculosis and healthcare associated infections. Self-medication with antibiotics in the community is driven by easy access, convenience, cost savings (no doctors’ fees) and the unregulated profit motive of pharmacy owners. Within the public healthcare sector, under-funded providers seek to balance hospital finances by over-prescribing, whilst poorly paid healthcare workers seek to augment meagre salaries. Meanwhile, weak monitoring and regulation of the public and private healthcare sectors further complicate the situation.

Unchecked, these supply and demand side incentives have led to a region awash with antibiotics and an incipient public health disaster. This disaster is comprised not only of untreatable infections, which are already happening, but also the unmeasured economic and social burden of the need for hospitalization and treatment with expensive second and third lines when the cheap first-line therapies fail.

Weak enforcement of regulations on the sale of antimicrobials and a lack of adherence to best practice in prescribing antimicrobials need to be urgently addressed. World Health Day in 2011 was ‘Antimicrobial resistance: no action today, no cure tomorrow’, and there is increasing global and regional advocacy for action against antimicrobial resistance. Such initiatives need to bring together all sectors including the public (whose expectations need to be adjusted), medical professionals (whose duty of care to future, as well as current, patients must be reinforced), and the drug sellers, pharmacists and pharmaceutical companies (who need to take their corporate social responsibilities seriously).

The prevention and control of healthcare associated infections is an essential function of all healthcare systems, yet infection control teams throughout the world struggle to encourage hand hygiene and ‘standard precautions’. In poorly resourced hospitals in low-and middle-income countries of Asia, where more than one patient may share a bed, infection control is usually a low priority. Although financial resources play a role, infection control is more about attitudes, working practices and governance structures. Within the constraints of affordable infrastructure and materials, health managers need to establish and monitor infection control standards, which should be publicly available core indicators of the quality of care for all healthcare institutions.

#### The internal human ecology

An exciting new area of exploration is the effect of disturbances of our own microbial ecology (the collection of microbes living on and inside us, known as our microbiome) on the emergence of both infectious and non-communicable diseases (NCDs). It is becoming increasingly clear that our internal microbial ecology plays a critical role in our health, influencing our susceptibility to both infectious diseases and NCDs, such as obesity, asthma and diabetes [34]. The Human Microbiome Project is part of the ongoing effort to explore this ecology. As knowledge accumulates, new insights will emerge of how changes in lifestyles and living conditions influence the emergence of new pathogens and new diseases — some of which may not yet be recognized as infectious in nature [35].

#### Disease surveillance and response

The International Health Regulations 2005 (IHR) place a requirement on member states to ensure that ‘core capacities’ in disease surveillance and response are ‘present and functioning throughout their territories by June 2012’ and to report ‘Public Health Emergencies of International Concern’ (PHEIC) to the WHO. Importantly, the IHR allows the WHO to unilaterally announce a PHEIC in the event of the WHO becoming aware of a public health emergency of international concern, if the implicated member state refuses to acknowledge the event or collaborate with the WHO.

A number of events and trends have converged to improve the reporting of EIDs in Asia. These include the revised IHR, the SARS and H5N1 epidemics, and advances in information technology. Whilst the Internet and social media have rendered it almost impossible to completely suppress information on emerging health crises, reporting first requires detection and the ability to detect EIDs at an early stage is still largely dependent on astute clinicians with close personal links to public health professionals. These human networks are crucial to successful surveillance and must not be neglected in the race to embrace new technologies.

Epidemic preparedness in the region has substantially improved as a result of SARS, H5N1 and pandemic influenza H1N1. The SARS outbreak is the most striking modern example of the aggressive and successful application of traditional public health interventions to contain an epidemic. The interventions included ‘source control’ (case-finding and isolation, quarantine of contacts), increasing social distance (such as by closing schools and cancelling mass gatherings), limiting spread of infection by domestic and international travellers (travel alerts, screening and restrictions), and infection control and hygiene measures (hand and cough hygiene, wearing masks or respirators). This success coloured the approaches taken to pandemic H1N1, with an unrealistic expectation by some that the pandemic could be contained. Informed by the eventful previous decade of EIDs the region is nevertheless much better placed to implement epidemic control interventions in a measured, thoughtful way. However, privatization, deregulation and provider diversification of the health sector is a regional trend that, without robust protection of public health interests, may have an adverse impact on disease surveillance systems.

#### Conclusion

A major shift is under way in the global centre of gravity, from West to East. Asia is becoming the dominant force of economic, social and environmental change, and whilst rapid development has brought many benefits, it has also resulted in widening health inequalities, increased social stratification, environmental degradation, increased migration and urbanization, and a concentration of people, food production and economic activity. These changes pose new risks to the populations’ health.

Amongst these health risks, infectious diseases remain critically important. Whilst inroads have been made, infectious diseases are dynamic and resilient, and continue to challenge local, national and global public health systems [36]. The recognition of the linkage between anthropogenic changes and disease emergence has resulted in repeated calls for a more holistic and interdisciplinary approach to the study of infectious diseases. The task ahead is to better understand how social and environmental changes occurring in Asia are altering the landscape of infectious disease risks and how future risks may be mitigated [37].

#### Acknowledgements

The author wishes to thank Dirk Pfeiffer for helpful discussions on livestock production systems in Asia.

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