Emerging infectious diseases in southeast Asia: regional challenges to control.
ABSTRACT Southeast Asia is a hotspot for emerging infectious diseases, including those with pandemic potential. Emerging infectious diseases have exacted heavy public health and economic tolls. Severe acute respiratory syndrome rapidly decimated the region's tourist industry. Influenza A H5N1 has had a profound effect on the poultry industry. The reasons why southeast Asia is at risk from emerging infectious diseases are complex. The region is home to dynamic systems in which biological, social, ecological, and technological processes interconnect in ways that enable microbes to exploit new ecological niches. These processes include population growth and movement, urbanisation, changes in food production, agriculture and land use, water and sanitation, and the effect of health systems through generation of drug resistance. Southeast Asia is home to about 600 million people residing in countries as diverse as Singapore, a city state with a gross domestic product (GDP) of US$37,500 per head, and Laos, until recently an overwhelmingly rural economy, with a GDP of US$890 per head. The regional challenges in control of emerging infectious diseases are formidable and range from influencing the factors that drive disease emergence, to making surveillance systems fit for purpose, and ensuring that regional governance mechanisms work effectively to improve control interventions.
- [show abstract] [hide abstract]
ABSTRACT: Between February and April, 1999, an outbreak of viral encephalitis occurred among pig-farmers in Malaysia. We report findings for the first three patients who died. Samples of tissue were taken at necropsy. Blood and cerebrospinal-fluid (CSF) samples taken before death were cultured for viruses, and tested for antibodies to viruses. The three pig-farmers presented with fever, headache, and altered level of consciousness. Myoclonus was present in two patients. There were signs of brainstem dysfunction with hypertension and tachycardia. Rapid deterioration led to irreversible hypotension and death. A virus causing syncytial formation of vero cells was cultured from the CSF of two patients after 5 days; the virus stained positively with antibodies against Hendra virus by indirect immunofluorescence. IgM capture ELISA showed that all three patients had IgM antibodies in CSF against Hendra viral antigens. Necropsy showed widespread microinfarction in the central nervous system and other organs resulting from vasculitis-induced thrombosis. There was no clinical evidence of pulmonary involvement. Inclusion bodies likely to be of viral origin were noted in neurons near vasculitic blood vessels. The causative agent was a previously undescribed paramyxovirus related to the Hendra virus. Close contact with infected pigs may be the source of the viral transmission. Clinically and epidemiologically the infection is distinct from infection by the Hendra virus. We propose that this Hendra-like virus was the cause of the outbreak of encephalitis in Malaysia.The Lancet 11/1999; 354(9186):1257-9. · 39.06 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Since it emerged in Japan in the 1870s, Japanese encephalitis has spread across Asia and has become the most important cause of epidemic encephalitis worldwide. Four genotypes of Japanese encephalitis virus (JEV) are presently recognized (representatives of genotypes I to III have been fully sequenced), but its origin is not known. We have determined the complete nucleotide and amino acid sequence of a genotype IV Indonesian isolate (JKT6468) which represents the oldest lineage, compared it with other fully sequenced genomes, and examined the geographical distribution of all known isolates. JKT6468 was the least similar, with nucleotide divergence ranging from 17.4 to 19.6% and amino acid divergence ranging from 4.7 to 6.5%. It included an unusual series of amino acids at the carboxy terminus of the core protein unlike that seen in other JEV strains. Three signature amino acids in the envelope protein (including E327 Leu-->Thr/Ser on the exposed lateral surface of the putative receptor binding domain) distinguished genotype IV strains from more recent genotypes. Analysis of all 290 JEV isolates for which sequence data are available showed that the Indonesia-Malaysia region has all genotypes of JEV circulating, whereas only more recent genotypes circulate in other areas (P < 0.0001). These results suggest that JEV originated from its ancestral virus in the Indonesia-Malaysia region and evolved there into the different genotypes which then spread across Asia. Our data, together with recent evidence on the origins of other emerging viruses, including dengue virus and Nipah virus, imply that tropical southeast Asia may be an important zone for emerging pathogens.Journal of Virology 03/2003; 77(5):3091-8. · 5.08 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Dengue is one of the most important emerging viruses, posing a threat to one-third of the global human population. Herein we show how the comparative analysis of gene sequence data has shed light on the origin and spread of dengue virus, as well as on the evolutionary processes that structure its genetic diversity. This reveals that dengue virus has a relatively recent evolutionary history, with the four serotypes originating approximately 1000 years ago and only establishing endemic transmission in humans in the last few hundred years. However, its place of origin remains uncertain as does the extent of genetic and phenotypic diversity present in the sylvatic (primate) transmission cycle. Although there is some evidence that viral strains differ in key phenotypic features such as virulence, and for positive selection at immunologically important sites, it seems likely that stochastic processes also play a major role in shaping viral genetic diversity, with lineage extinction a common occurrence. A more complete understanding of the evolution and epidemiology of dengue virus, particularly with respect to the aetiology of severe disease, will require large-scale prospective studies and the comparative analysis of complete genome sequences.Infection Genetics and Evolution 06/2003; 3(1):19-28. · 2.77 Impact Factor
www.thelancet.com Vol 377 February 12, 2011 599
Lancet 2011; 377: 599–609
January 25, 2011
See Comment page 534
See Comment Lancet 2011;
This is the third in a Series of
six papers on health in
Communicable Diseases Policy
Research Group (CDPRG),
London School of Hygiene and
Tropical Medicine, Faculty of
Tropical Medicine, Mahidol
Thailand (Prof R J Coker MD,
B M Hunter MSc, J W Rudge PhD,
M Liverani MSc,
P Hanvoravongchai MD)
Prof Richard J Coker,
Communicable Diseases Policy
Research Group (CDPRG),
London School of Hygiene and
Tropical Medicine, Anek Prasong
Building, Faculty of Tropical
Medicine, Mahidol University,
420/6 Rajvithi Road,
Bangkok 10400, Thailand
Health in Southeast Asia 3
Emerging infectious diseases in southeast Asia: regional
challenges to control
Richard J Coker, Benjamin M Hunter, James W Rudge, Marco Liverani, Piya Hanvoravongchai
Southeast Asia is a hotspot for emerging infectious diseases, including those with pandemic potential. Emerging
infectious diseases have exacted heavy public health and economic tolls. Severe acute respiratory syndrome rapidly
decimated the region’s tourist industry. Infl uenza A H5N1 has had a profound eff ect on the poultry industry. The
reasons why southeast Asia is at risk from emerging infectious diseases are complex. The region is home to dynamic
systems in which biological, social, ecological, and technological processes interconnect in ways that enable microbes
to exploit new ecological niches. These processes include population growth and movement, urbanisation, changes in
food production, agriculture and land use, water and sanitation, and the eff ect of health systems through generation of
drug resistance. Southeast Asia is home to about 600 million people residing in countries as diverse as Singapore, a
city state with a gross domestic product (GDP) of US$37 500 per head, and Laos, until recently an overwhelmingly
rural economy, with a GDP of US$890 per head. The regional challenges in control of emerging infectious diseases are
formidable and range from infl uencing the factors that drive disease emergence, to making surveillance systems fi t for
purpose, and ensuring that regional governance mechanisms work eff ectively to improve control interventions.
Emerging infectious diseases result from complex,
dynamic systems in which biological, social, ecological,
and technological processes interconnect. Southeast Asia
is a loosely defi ned geopolitical region that is characterised
and shaped by diff ering environmental, ecological, and
economic factors. These factors are discussed in more
detail in other reports in this Series. As a consequence, the
region shoulders a great diversity of communicable disease
and, closely associated with development, a heavy burden
in countries with the lowest incomes (see fi gure).1 The
region has been at the centre of global attention regarding
emerging infectious diseases, with the threat of diseases
with pandemic potential receiving particular attention.
Although the focus of this paper is emerging infectious
diseases, as can be seen in the fi gure, the burden of
infectious diseases is substantial. In low-income countries
in particular, respiratory infections and diarrhoeal diseases
are especially important. For the purposes of this paper, we
defi ne southeast Asia as the ten member countries of the
Association of Southeast Asian Nations (ASEAN), a region
with growing geopolitical infl uence in view of Asia’s global
economic ascendancy. The ASEAN countries are Brunei,
Cambodia, Indonesia, Laos, Malaysia, Myanmar, the
Philippines, Singapore, Thailand, and Vietnam.
Defi nitions of emerging infectious diseases vary—for
example, to refl ect whether concepts such as drug
• Southeast Asia is a diverse region that is undergoing rapid
social, environmental, and demographic change.
• The emergence of new ecological niches means that the
region is likely to remain a hotspot for emerging
• Governance of infectious disease control is challenging,
with overlapping institutional roles and responsibilities.
The region also is politically complex, with some
intranational and international tensions that have the
potential to further hinder control.
• There has been substantial investment in surveillance
capacity in recent years, but it remains weak in many areas.
• Research in the region that practically informs policy and
practice is scarce. Research areas demanding attention
include the development of predictive surveillance
(including the potential risks associated with social and
environmental changes) and priority setting within
health systems to allow response to surges in demand and
to improve equity, eff ectiveness, and effi ciency.
Search strategy and selection criteria
We searched peer-reviewed English language literature
through PubMed and grey literature published since 2000.
We focused on factors leading to the emergence of infectious
diseases in Association of Southeast Asian Nations countries,
surveillance capacity, and governance of control systems. We
searched institutional websites (for example, WHO, the Food
and Agriculture Organization, the World Organisation for
Animal Health, and donor agencies), and analysed primary
data derived from these sources to provide an overview of
crucially important issues related to emerging infectious
diseases in southeast Asia during the past decade. Data were
analysed to identify trends for upstream driving forces for
emerging infectious diseases in the region. The ongoing
portfolio of research of the London School of Hygiene and
Tropical Medicine’s Communicable Diseases Policy Research
Group based in the region was also reviewed.
For the Communicable Diseases
Policy Research Group see
www.thelancet.com Vol 377 February 12, 2011
resistance are included.2,3 For the purposes of this report
we use the WHO defi nition of diseases that are “newly
recognised, newly evolved or occurred previously but
have shown an increase in incidence or expansion of
geographical, vector or host range”4 and include
pathogens showing drug resistance within this defi nition.
The table summarises several infections that have
attracted attention in recent years.
We review the past decade’s experience of emerging
infectious diseases in southeast Asia and refl ect on the
epidemiological driving forces behind these diseases,
the regional diversity regarding human and animal
public health capacity, progress and shortfalls in
regional disease surveillance, and the challenges to
governance faced at national and international levels.
We draw attention to what we believe are crucially
important challenges, briefl y provide case studies to
illustrate some of these challenges, and off er insights
into what steps might be taken to improve control of
emerging infectious diseases.
The burden and diversity of emerging infectious
During the past decade, novel viruses, particularly those
causing severe acute respiratory syndrome (SARS) and
avian infl uenza A H5N1, have attracted international
concern, attention, and investment in southeast Asia.
These two diseases, although undoubtedly exerting major
public health and economic burdens, represent only part
of a rich tapestry of many pathogens that have emerged
to pose a public health threat within the region in recent
years (table and panel 1).5–20 Recent outbreaks of Nipah
virus and artemisinin-resistant Plasmodium falciparum,
for example, both of which have emerged within the
region itself, have also focused national, regional, and
international attention on the threat posed by emerging
infectious diseases, and in particular on southeast Asia
as the epicentre of these diseases.
The role of southeast Asia as a hotspot for emerging
diseases is further illustrated by the less recent but
certainly no less important emergence of new cholera
and dengue variants that continue to greatly aff ect
both regional and global health. The variant of
Vibrio cholerae 01 El Tor causing the present (seventh)
pandemic fi rst emerged in Indonesia in 1961. Moreover,
the fi rst major outbreaks of the haemorrhagic form of
dengue were reported in Manila, Philippines, and
Bangkok, Thailand, in the 1950s, and the southeast Asian
strains have contributed greatly to global spread of
dengue—causing outbreaks of haemorrhagic disease
throughout the Americas, for example.21 Japanese
encephalitis, another arbovirus that is highly endemic to
southeast Asia, is thought to have evolved in the region
and has subsequently spread across Asia and to parts of
Australia.22 Other threats of notable concern to the region,
but receiving little attention, include increasing rates of
antibiotic resistance among enteric pathogens such as
Campylobacter23 and increasing incidence of food-borne
trematodiases in parts of southeast Asia.
Despite southeast Asia’s importance with respect to
emerging infectious diseases, frailties and diff erences in
surveillance systems within the region make estimation
of the burden and diversity of disease and any cross-
country comparisons diffi cult. As we note in this report,
the likelihood of widespread under-reporting of emerging
infectious diseases means that knowledge is scarce and
prevention and response hampered. But perhaps a
greater challenge is determination of the risk of emerging
infectious diseases that arises from infl uences within the
region, and development of strategies that address both
public health prevention, containment, and mitigation
imperatives and socioeconomic realities.
The consequences of emerging infectious diseases in
southeast Asia stretch far beyond a narrow purview of
public health. The estimated cost of SARS to east and
southeast Asia was US$18 billion, which is roughly
US$2 million per person infected.24 In southeast Asia, the
sudden collapse in demand for the service industry was a
dominant feature in this cost, particularly in view of a
tourist industry reliant on the 35 million tourists arriving
every year from outside the region.25 Indeed, the relation
between public health and socioeconomic eff ects is by no
means linear. Bovine spongiform encephalopathy and
variant Creutzfeldt-Jakob disease in the UK illustrated this
eff ect. Fear, anxiety, and changes in behaviour and the
eff ect on the tourist industry have unpredictable
consequences. Before 2009, the World Bank estimated a
possible global cost of an infl uenza pandemic at around
Figure: The burden of communicable disease in southeast Asian countries, 2004
Data are from WHO Global Burden of Disease, 2004 update.1 DALYs=disability-adjusted life-years. STDs=sexually
0 5000 10 00015 000
Age-standardised DALYs per 100 000 population
STDs excluding HIV
Intestinal nematode infections
www.thelancet.com Vol 377 February 12, 2011 601
US$1·25 to 2 trillion.26 The Asian Development Bank
estimated a shock to demand might cost southeast Asia up
to US$283 billion.27 Moreover, the costs of emerging
infectious diseases, including pandemics, do not fall
evenly. Although emerging infectious diseases have until
now disproportionately aff ected low-income countries,1
and the poorest within society were aff ected the most,28
pandemics have the potential to disrupt highly inter-
connected and high-income areas such as Singapore.27,29
The economic consequences of H5N1 infl uenza have
been diff erent from those of SARS in southeast Asia. The
region’s tourist industry collapsed overnight as a result
of SARS. Although aff ected, the industry has been aff ected
less by H5N1. The poultry industry, by contrast, was
profoundly aff ected. Control policies during the 2003–04
H5N1 outbreak in Vietnam led to the culling of 45 million
birds at an estimated cost of almost US$118 million.30
Furthermore, insuffi cient reimburse ment after a ban on
the sale of so-called backyard poultry in Vietnam lowered
the household income for poor families disproportionately
by com parison with wealthier families.26 In Thailand,
where the highly industrialised poultry export market is
an important contributor to the national economy, exports
were banned.31 In 2003, poultry meat exports were worth
US$597·6 million. A year later, they had had fallen by 93%
to US$43·5 million.32 Avian infl uenza continues to exact
an economic strain in the region, with new cases in
poultry or wild birds reported this year from Cambodia,
Vietnam, Laos, and Myanmar (Indonesia is endemic for
H5N1 in birds, but does not report current outbreaks).
Surprisingly, the potential economic eff ect of other
emerging infectious diseases in southeast Asia, and
analyses of the operational capacity of health systems to
respond, have received little robust research attention.
Important factors leading to the emergence of
Driving forces in southeast Asia
Southeast Asia is a hotspot for emerging infectious
diseases—in particular, zoonotic and vector-borne
diseases—as a result of many factors including population
growth, mobility, and urbanisation, and environmental
changes such as agriculture and livestock intensifi cation,
deforestation, and climate change. Many, if not all, of
these interlinked driving forces, although occurring in
other parts of the world, have particularly important
eff ects on emerging infectious diseases in southeast Asia
(web appendix p 1).2,3,33 Indeed, the factors that coalesce in
Avian infl uenza A H5N1 Zoonotic (close contact with poultry)325 reported cases, 224 deaths in Indonesia, Vietnam, Thailand, Cambodia, Laos, and
5290 reported cases, eight deaths in all ten countries6
Pandemic infl uenza A H1N1
Respiratory331 reported probable cases, 44 deaths in Singapore, Vietnam, Thailand, Malaysia, and
First known human cases in Malaysia; 276 cases, 106 deaths in Malaysia and Singapore8 Nipah virus
Zoonotic (close contact with pigs)
Vector-borneEndemic in many southeast Asian countries; re-emerged in Singapore (2008),
Malaysia (2007),9 Thailand (2009), and Indonesia (2010)
Originated in southeast Asia; 398 340 cases and 1596 deaths in 2008 with high burden
in Indonesia, Vietnam, Thailand, Malaysia, the Philippines, Myanmar, and Cambodia;
estimated 253 000 DALYs lost in 20041
Only 68 reported cases in Thailand in 2009;10 estimated 243 000 DALYs lost in 20041
587 cases and deaths in 2009 in Indonesia, the Philippines, Vietnam, Myanmar, and
High adult HIV prevalence (more than 0·5%) in Thailand, Cambodia, and Myanmar, with
more than 200 000 HIV-positive people in Thailand, Vietnam, Indonesia, and Myanmar;11
estimated 2 952 000 DALYs lost in 20041
Case reports from Thailand and Vietnam12
5697 cases and 83 deaths in 2009 with high burden in Thailand and reported cases in
Indonesia and Myanmar10
Dengue fever Vector-borne
Vector-borne and zoonotic
Zoonotic (bite or scratch from rabid
Sexual, injecting drug use, verticalHIV/AIDS
Zoonotic (close contact with pigs)
Zoonotic (skin contact with urine of
MDR tuberculosisRespiratory 2332 cases in 2008;13 high-burden countries are the Philippines, Myanmar, Indonesia,
Detected in Myanmar, the Philippines, Singapore, Thailand, and Vietnam13
Documented on Cambodia’s border with Thailand14
MDR Plasmodium falciparum
SARS=severe acute respiratory syndrome. DALYs=disability-adjusted life-years. MDR=multidrug resistant. XDR=extensively drug resistant.
Table: Summary of selected emerging infectious diseases in southeast Asia
See Online for webappendix
www.thelancet.com Vol 377 February 12, 2011
east and southeast Asia to increase the risk of emerging
infectious diseases can be considered at three levels: (1) as
a region containing diverse zoonotic and vector-borne
pathogens, and thus a primary source of emerging
infectious disease; (2) as a region in which the high
density, proximity, and mobility of human beings and
animal reservoirs provide fertile conditions for
transmission between species, within human populations,
and across geographic areas; and (3) as a region with
ecological factors that allow rapid pathogen mutation and
host adaptation—for example, Dengue, reassortments of
infl uenza virus, and emergence of drug resistance.34–36
Population growth and urbanisation
Human population growth and increasing density are
important independent predictors of emerging infectious
diseases.2 The population in southeast Asia, which is
currently estimated at around 580 million, has increased
by more than 30% since 1990.37 Increasing population
density not only aff ects the spread of infectious diseases
directly (eg, through increased human-to-human
contact), but also underpins many other ecological
driving forces such as changing land use, agriculture,
and livestock intensifi cation.38
In addition to rapid population growth, southeast Asia
is rapidly becoming more urbanised, with low-income
countries seeing the most striking changes. Around
48% of people in the region live in urban areas, a fi gure
which is expected to grow to more than 70% by 2050
(webappendix p 1).37 Urbanisation is associated with
changes in social structures, increased personal mobility,
and extended and changing social networks.39 It is also a
driving force behind some vector-borne diseases—for
example, dengue, which has seen a resurgence in
southeast Asia during the past 50 years. This resurgence
has been linked to the establishment of (often
impoverished) periurban areas in which the collection
and storage of water, because of a lack of reliable water
and sanitation systems and the accumulation of social
detritus such as used tyres, provide breeding sites for
Aedes aegypti mosquitoes.21
Birth rates, which are highest in the poorest countries
in the region, also have consequences for infectious
disease transmission because of the eff ect of immuno-
logically naive individuals who perpetuate epidemics.
Fortunately, the demographic shift towards decreased
birth and mortality rates across southeast Asia might help
to lower the transmission of some diseases, and there is
evidence of such an eff ect on dengue in Thailand.40
Population movements and animal trade
Increasing regional population mobility, including both
documented and undocumented travel as well as
increases in international population movements across
national boundaries, is an important feature of southeast
Asia. The Mekong Basin subregion, which includes
Thailand, Cambodia, Laos, Vietnam, Myanmar, and
Panel 1: A brief overview of selected newly emerging infectious diseases in
In recent decades, the only major infectious disease in man to have probably emerged in
southeast Asia was severe febrile encephalitis during infection with Nipah virus. Occurring in
peninsular Malaysia and Singapore in late 1998 to early 1999, the outbreak resulted in the
deaths of more than 100 people in these two countries (at a case fatality rate of
around 40%),8 which is twice as many as were killed by severe acute respiratory
syndrome (SARS) across all of southeast Asia and just under half as many as have died of
avian infl uenza A H5N1. Most of those infected worked in the pig farming and meat
production industries, refl ecting the major form of transmission, which was close contact
between pigs and human beings. Despite eventual containment of the outbreak through a
mass cull of more than a million pigs, a related virus has since emerged outside southeast
Asia, causing outbreaks in Bangladesh and India.
In 2003, southeast Asia’s unique combination of strong links with other Asian countries
alongside a multitude of intercontinental connections (three of the world’s 30 busiest
airports are now found in southeast Asia—Bangkok, Jakarta, and Singapore) facilitated
the regional and global spread of the SARS coronavirus from its origins in southern China,
a close neighbour. Guests infected in a hotel in Hong Kong (where an infected doctor
from China was staying) unknowingly carried the virus to several countries including
Vietnam and Singapore.15 Outbreaks occurred in both of these countries and cases were
reported throughout the region, although Singapore was the most severely aff ected with
33 deaths compared with 11 across the rest of southeast Asia.7 Singapore was also
implicated in international transmission to outside the region. Although the global
outbreak ended in July, 2003, a further laboratory-acquired infection was reported in
Singapore in September, 2003.
H5N1 infl uenza
In the same year as SARS spread through southeast Asia, the region began to experience
outbreaks of another emerging infectious disease, H5N1 infl uenza, which had again
spread from southern China.16 Although the very high mortality in domestic poultry
(approaching 100%) was alarming, the number of human infections that were occurring
and the deaths of many of those infected (human case fatality in southeast Asia was just
under 70%)5 caused greater concern. The previous rapid worldwide dissemination of the
SARS coronavirus fuelled fears that the H5N1 virus, were it to become readily
transmissible between humans and retain some of its pathogenic potential, could spread
rapidly and result in an infl uenza pandemic that might kill millions, result in untold
economic disruption, and threaten global security.17 Despite these grave concerns, the
H5N1 virus has yet to cause an infl uenza pandemic owing to an inability to achieve
sustained human-to-human spread (although there is evidence to support some
human-to-human transmission events).18,19 However, the threat still remains. The virus
continues to circulate in wild birds worldwide, causing outbreaks in poultry in several
southeast Asian countries, and, in 2010, cases in human beings have been reported in
southeast Asia in Cambodia, Indonesia, and Vietnam.
Artemisinin-resistant falciparum malaria
Reports of reduced Plasmodium falciparum clearance rates during treatment with
artemisinin (in combination therapy as well as monotherapy) have surfaced in southeast
Asia, namely on the Thailand–Cambodia border, since 2004.14 These reports have attracted
much regional and international concern, especially in view of southeast Asia’s historical
role in the emergence and spread of parasite resistance to chloroquine and sulfadoxine–
pyrimethamine, and the reliance of the global Roll Back Malaria campaign on artemisinin
combination therapy. Although a containment programme, currently funded by the Bill &
Melinda Gates Foundation, is in place, there is an acceptance that “the actual geographic
extent of resistance is unknown”.20
www.thelancet.com Vol 377 February 12, 2011 603
China, has seen a sharp increase in cross-border
migration in recent years. Much of this migration is
driven by poverty, with migrant workers moving from
the low-income countries of Laos, Cambodia, and
Myanmar to Thailand, a middle-income country. Thailand
is estimated to have 1·5–2 million immigrants from
neighbouring countries, and about 150 000 refugees.
Large-scale migration of economic and political refugees,
including the frequent movements of hill tribe
populations along with their livestock, present substantial
challenges to cross-border disease control in the Mekong
Basin subregion. Furthermore, undocumented migrants
often live in unhygienic and overcrowded conditions
(particularly in camps such as those along the Thailand–
Myanmar border) with poor access to health services,
with infectious diseases such as malaria being an
important cause of morbidity and death.14,41–43
In addition to human movements, increased cross-
border trade of livestock and wildlife is also a concern.
Trading centres, for example, can act as mixing bowls
for “humans and dozens of other species before they
are shipped to other markets, sold locally, or even freed
and sent back into the wild”.44 Data for wildlife trade is
scarce, although some have estimated that in east and
southeast Asia, tens of millions of wild animals cross
borders each year regionally and to more distant
countries around the world for use as food, pets, or in
traditional medicine.44 Figures suggest that the export
of many diff erent species of wild animals increased
between 1998 and 2007, although the licit export of
birds fell substantially after major importers such as
the European Union imposed restrictions in response
to H5N1 infl uenza. Along with trade, the natural
movements of migratory birds and bats within, to, and
from the region are also a key infl uence for several
emerging infectious diseases such as H5N1 infl uenza,
Japanese encephalitis, and Nipah virus.
Water and sanitation
In terms of population coverage, water and sanitation
systems are improving in southeast Asia, with the region
generally on track to meet the Millennium Development
Goal targets. This progress is encouraging in view of the
association between water and sanitation systems and
the burden of diarrhoeal diseases across southeast Asia
in low-income countries (webappendix p 2), along with
links to vector-borne diseases, as we have mentioned.
However, population growth and urbanisation mean that
the number of people in southeast Asia using unimproved
sanitation and drinking water systems in urban areas is
actually increasing, having risen by 20 million between
1990 and 2006.
Agriculture and changing land use
Human-induced changes in land use are key driving
forces of emerging infectious diseases and also modify
the transmission of endemic infections.33 Agriculture
occupies around 25% of the land in southeast Asia, with
the total agricultural area having increased by more than
8% between 1990 and 2008 (webappendix p 1). Moreover,
there has been a particularly large increase, of more than
30% across the region, in the land area used for rice
cultivation.32 Development of rice paddies can promote
transmission of vector-borne diseases such as Japanese
encephalitis through their role as vector-breeding sites
and by attracting water birds, which are the natural
reservoir of Japanese encephalitis. Transmission between
birds and mosquitoes is further amplifi ed by transmission
in pigs.21 Countries such as Cambodia, Indonesia, Laos,
and Myanmar are at risk of increases in Japanese
encephalitis because of the combination of intensifi ed
rice and pig farming and the absence of vaccination
programmes and surveillance.45 In addition to an
increased potential for transmission of Japanese
encephalitis, the attraction of various birds to rice paddies
has also been associated with increased risk of H5N1
outbreaks in Thailand and Vietnam.46
Deforestation is continuing across most countries in
the region (webappendix p 1). Human encroachment and
fragmentation of wildlife habitats through processes
such as deforestation increase interactions between
wildlife, human beings, and livestock, and thus the
potential for pathogens to cross species barriers. In
Malaysia, changes in movements and densities of fruit
bats due to deforestation, wildfi res, and plantation of
fruit orchards, along with the intensifi cation of pig
farming close to fruit-bat habitats, have all been postulated
as infl uences for the emergence of Nipah virus as a
zoonosis in Malaysia.8,33,47
Intensive livestock production is increasingly prevalent
across southeast Asia. The density of poultry has at least
doubled in most countries between 1990 and 2008, and
increased more than three-fold in countries such as
Myanmar, Laos, and Brunei (webappendix p 1).
Increased poultry density is associated with the
cumulative number of H5N1 cases in human beings at
country level across the region (webappendix p 3).
Although backyard and village farms remain the
predominant environment for poultry producers in
most low-income countries in southeast Asia, industrial
production systems dominate in others, such as
Thailand.30,48 Where poultry production is in a backyard
setting or is on a small scale, investment in biosecurity
is likely to be low and ill-coordinated. Many species
often coexist and the potential for cross-species
transmission can be increased. However, as intensive
production of single species in large-scale industrial and
commercial sectors is becoming more dominant,
although this setting might reduce the risk of cross-
species infection, these sites might also act as amplifi ers
of disease during the emergence of large-scale outbreaks.
Moreover, cross-infection can still occur within the
www.thelancet.com Vol 377 February 12, 2011
marketplace, where economic imperatives can over-ride
public health concerns.39
In concert with poultry production, pig farming is also
intensifying across the region, with densities having at
least doubled since 1990 in Myanmar, Laos, Vietnam,
Indonesia, and the Philippines (webappendix p 1). This
trend is arguably a cause for concern in view of the role
of pigs in the transmission of zoonoses such as Nipah
virus, Japanese encephalitis, and infl uenza.
Vector-borne and waterborne diseases are both strongly
aff ected by climate. For example, the strength of El Niño
was a predictor for dengue outbreaks in Thailand49 and
Vietnam.50 Since arthropod vectors tend to be most active
at high temperatures, and because water scarcity during
droughts often leads to poor sanitation, climate change
can be expected to drive the spread of vector-borne
diseases and diarrhoeal illnesses in southeast Asia.
In addition to the aforementioned demographic and
environmental factors, which can drive the emergence of
novel diseases and increase the incidence, prevalence, or
geographic scope of existing ones, the importance of
public health system factors as infl uences, in particular
for the emergence of newly resistant strains, should not
be underestimated. Irrational drug use, frail public health
systems,34 and the wide availability of counterfeit and
substandard drugs are factors with particular relevance
in southeast Asia.51
During the past fi ve decades, southeast Asia has been
the epicentre of the evolution and spread of resistance to
all important classes of antimalarial drugs. In the 1950s
and 1960s, the Thailand–Cambodia border was the site
of emergence of chloroquine and sulfadoxine–pyri-
methamine resistance in P falciparum. This resistance
subsequently spread across Asia and then Africa. Within
the past 10 years, reduced susceptibility to the artemisinins
has been documented in Cambodia,52 and concerns that
it could spread have raised much concern within the
international community. Surveillance information about
the scale of artemisinin-resistant malaria in the region
remains poor, however. Likewise, surveillance data for
drug-resistant tuberculosis in the region are scarce,
especially for low-income countries (Laos, for example,
reports no multidrug-resistant cases).
Surveillance systems are the foundation on which disease
control systems sit. They can serve several functions
including anticipation of the emergence of diseases,
support of outbreak responses, and facilitation of the
monitoring and evaluation of responses. Although the
observation and analyses of factors can be used to predict
the emergence of infectious diseases, currently such
predictive surveillance lacks specifi city and sensitivity. As
with any surveillance system, the completeness of data is
problematic. For example, no cases of human Japanese
encephalitis or leptospirosis were reported from either
Laos or Cambodia during 2009, and no cases of rabies in
human beings were reported from Laos in 2009, even
though all diseases were reported in other neighbouring
countries and the likelihood of disease seems high.
With most human pathogens originating as zoonoses,
surveillance systems have until now relied on surveillance
of animals and human beings. However, as in other
resource-poor regions, capacity for animal health
surveillance in southeast Asia is underdeveloped.53 Major
constraints include the absence of specifi c government
policies and legal frameworks for surveillance and control
of zoonoses, as well as inadequate resources, insuffi cient
animal–human public health cooperation, coordination,
and collaboration, frail laboratory facilities, and weak and
disconnected reporting systems.54 The emergence
of SARS and the H5N1 and H1N1 (2009) viruses focused
minds and brought investment. In Laos, for example,
until 2004 there was almost no national infrastructure for
communicable disease control.55 Initially, the Law on
Hygiene, Disease Prevention and Health Promotion (2001)
was the only law that addressed communicable diseases,
and it principally applied to prevention rather than control
and response.56 In the wake of H5N1 infl uenza outbreaks,
however, the government established several new
institutions to strengthen national capacities, including a
National Coordination Committee on Communicable
Diseases, a National Emerging Infectious Disease Control
Offi ce, and a Centre for Laboratory and Epidemiology that
has recently been designated the national focal point for
the implementation of the International Health
Regulations.56 Similarly, the governments of Vietnam,
Thailand, Indonesia, Cambodia, Malaysia, and the
Philippines have all set up new institutional bodies,
strengthened diagnostic laboratory capacity, and improved
coordination mechanisms. Although gaps in national
planning and surveillance systems persist, countries in
southeast Asia have made substantial progress towards
eff ective prevention and control of infectious diseases.57
Crucially, surveillance systems for infl uenza have
started to integrate elements of animal health, particularly
poultry-related incidents.57 For example, rapid response
teams have been mobilised and trained to improve
community-based surveillance in 331 districts in
Indonesia. In Laos and Cambodia, a substantial amount
of donor funding has been used to support pandemic
preparedness and responses, including development of
surveillance systems. Laboratory capacity to handle
infl uenza viruses has improved—for example, through
the building of biosafety level 3 laboratories in Indonesia
and Cambodia for virus sequencing.57
Regional public health institutions have become
sensitive to the threat posed by zoonoses. ASEAN member
states have recently endorsed a Regional Mechanism on
Animal Health and Zoonoses, to develop a unifi ed
www.thelancet.com Vol 377 February 12, 2011 605
framework against threats from animal diseases.58
Moreover, the integration of animal and human health
has been at the centre of WHO’s Asia-Pacifi c Strategy on
Emerging Diseases—an ambitious strategic framework
that aims to develop mechanisms for information sharing
between the animal and human health sectors both at
regional and country levels, in partnership with the Food
and Agriculture Organization and the World Organization
for Animal Health.59 The overlapping functions of some
regional institutions and their substantially diff erent
geographic coverages are described on webappendix p 4.
These initiatives are emerging in a complex regional
environment, however. At a national level, thriving private
health-care sectors in many countries increasingly pose
challenges to reporting systems, with some being either
unwilling or unable to provide information.60 Similar
challenges arise from decentralised health systems—for
example, in Indonesia and the Philippines, where local
health authorities have become less active in case reporting
compared with other countries.61 Where vertical disease-
specifi c surveillance programmes have been developed,
such as in Cambodia, there is a risk that parallel surveillance
and laboratory testing systems, especially those funded
through investments related to pandemic infl uenza
preparedness or other global health initiatives, draw on
limited existing capacity and contribute to a duplication of
eff orts and ineffi cient use of resources.62 In addition to the
regional initiatives that we have described, several col-
laborative surveillance programmes and support structures
exist, with input from the Western Pacifi c Regional Offi ce
and the South East Asia Regional Offi ce of WHO (which
themselves split southeast Asia along political lines that
are diff erent from those of ASEAN). These programmes
include the Mekong Basin Disease Surveillance network
(an innovative cross-border initiative; panel 2), the
Southeast Asian Medical Information Centre, ASEAN, and
the Asia-Pacifi c Economic Cooperation forum.
In an eff ort to address some of the weaknesses in
surveillance in southeast Asia, several collaborative
programmes for infectious disease research have been
undertaken in association with Western countries. Some
of these collaborations are very well integrated into the
existing health system structure—for example, the Institut
Pasteur, whose facilities have become national institutes
in several major provinces of Vietnam. The Institut Pasteur
network also includes a facility in Phnom Penh in close
collaboration with the Ministry of Health in Cambodia,
and another is under construction in Laos in formal
association with the Laotian Ministry of Health. In
Thailand, the Ministry of Public Health is also actively
collaborating with the US Centers for Disease Control and
Prevention to work on emerging infectious and tropical
diseases, and the Thai and US armies have a collaborative
infectious disease research laboratory, the Armed Forces
Research Institute of Medical Sciences, which developed
from a cholera research laboratory in 1958.66 The Wellcome
Trust centres in Thailand, Vietnam, and Laos have had a
longstanding presence, and the London School of Hygiene
and Tropical Medicine has a research collaborating centre
in the region, in Thailand. Indonesia’s recent experience
of collaborating with external infectious disease
laboratories has been more problematic. Before closing
down in 2008, the US Naval Medical Research Unit 2 in
Indonesia was charged with political accusations of
off ering questionable benefi t to Indonesians during its
30 years of operation and of alleged improper use and
export of viral specimens67—themes that were to resonate
globally with the ongoing debate about the sharing of
biological materials and benefi ts that might accrue from
the development of vaccines (panel 3).
Capacity for health-service response
As in many developing areas of the world, veterinary
services in several southeast Asian countries are weak,
and biosecurity in animal farms is poor. Although
Panel 2: The Mekong Basin Disease Surveillance initiative—cross-border surveillance
The Mekong Basin Disease Surveillance (MBDS) initiative was established in 1999 with
the core values of “mutual trust, transparency [and] cooperative spirit”.63 Encompassing
Cambodia, Laos, Myanmar, Thailand, and Vietnam as well as China’s Yunnan province and
Guangxi Zhuang autonomous region, the MBDS network straddles both the WHO South
East Asia Regional Offi ce and Western Pacifi c Regional Offi ce regions, aiming to facilitate
cross-border cooperation in surveillance and control of infectious disease.
A network of cross-border surveillance collaborations underpins the project, each consisting
of two community-based surveillance sites, one on each side of the border, which report
cases from a defi ned list of infectious diseases (webappendix p 6).
These sites have been responsible for notable successes of the MBDS—for example, the
discovery of a Laotian infected with infl uenza A H5N1 in Thailand and the subsequent joint
Lao–Thai investigation. Another example was the joint Lao–Thai investigation of a cholera
outbreak that spread from Thailand to Laos with identifi cation of the source, enabling
coordinated control measures to be implemented. The scope of the project extends beyond
joint monitoring and investigations. For example, cross-border medical care from Thailand
was dispatched to Myanmar after cyclone Nargis in 2008. The completion of a regional
tabletop pandemic preparedness exercise in Siem Reap, Cambodia, in 2007, further serves as
an example of international collaboration through the initiative.
The signing of a new Memorandum of Understanding in 200764 refl ected these successes,
and the latest MBDS Action Plan63 seeks to further cross-border cooperation with
activities that include:
• Establishment of two new cross-border sites per country per year.
• Regular meetings between participants and leaders at cross-border sites to discuss
progress and share experiences.
• Annual documentation of outbreak investigations or exercises at each site.
• Ensuring suffi cient clinical capacity, health-care workers, and personal protective
equipment as well as adequate capacity for patient isolation and quarantine.
Successes of the MBDS initiative have shown the potential for collaborative eff orts
between resource-poor nations to meet WHO’s 2005 International Health Regulations.
MBDS might be a potential model to establish similar networks in other regions
worldwide and to strengthen existing informal collaborations in regions with national
tensions, such as the Middle East Consortium on Infectious Disease Surveillance (Israel,
Jordan, and the Palestinian Authority).65
www.thelancet.com Vol 377 February 12, 2011
Thailand remains a regional example of success in the
control of H5N1 virus outbreaks in birds, and has
invested heavily in biosecurity, the animal health systems
of low-income countries in the region are weak.72,73
In terms of health-care resources for treatment of
emerging infectious diseases in human patients, low-
income countries face major constraints. For example,
three countries in the region (Laos, Cambodia, and
Indonesia) spend less per head than has been estimated
to be necessary for health system functions to meet the
Millennium Development Goals.57 There are substantial
shortages of human resources in some countries in the
region.74 The density of health-care professionals in fi ve of
the ten countries (Cambodia, Indonesia, Laos, Myanmar,
and Vietnam) is lower than the level defi ned by WHO as
adequate. The availability of health-care facilities as
proxied by number of hospital beds per head is also very
low in Laos, Cambodia, and Indonesia.75 With existing
weakness in health system capacity, many countries in
southeast Asia are at risk of being unable to adequately
respond to emerging threats from new and re-emerging
diseases or to surges in demand that might accompany
these diseases. A study that included fi ve southeast Asian
countries showed that wide disparities exist in resource
capacity not only in aggregate between countries, but also
within countries. The northeast of Thailand has, for
example, gaps in some health service resources that are
more similar to the distribution in Laos and Cambodia
than that of central Thailand. Ongoing research within
our group suggests that these disparities probably result
in inequitable rates of preventable mortality from
emerging infectious diseases.60,76
Regional coordination and support
As we have noted, there have been important initiatives
aimed at strengthening the control of emerging infectious
diseases regionally. To diff ering degrees, ASEAN, the
Ayeyawady-Chao Phraya-Mekong Economic Cooperation
Strategy, and the Asia-Pacifi c Economic Cooperation
forum have all endorsed transnational cooperation in joint
action with the WHO South East Asia and Western Pacifi c
Regional Offi ces. Beyond surveillance, for example, the
ASEAN Secretariat has managed a Singapore-based
regional stockpile of 500 000 courses of antiviral drugs for
the benefi t of ASEAN member states (a regional
collaborative stockpile that European institutions were
unable to achieve). This initiative complements another
supply of an additional 500 000 treatment courses that
have already been distributed to ASEAN member states
on the basis of population size. Another example of
regional solidarity is the support given on the international
stage of the UN by states such as Thailand that are
sympathetic to Indonesia’s stance on virus sharing.
The implementation of programmes for emerging
infectious diseases in southeast Asia owes much to the
fi nancial and technical assistance of donor countries,
private philanthropists, or development agencies such as
the Asian Development Bank, the World Bank, the Global
Fund, and the Rockefeller Foundation. The ASEAN
stockpiles of antiviral drugs, for instance, were funded by
the Japanese Government with a US$30 million grant
within the wider scheme of the ASEAN-Japan Integration
Fund. Additionally, the ASEAN Secretariat has long
received support from the Australian Government
through AusAid, the US Government, and the European
Union, and the Mekong Basin Disease Surveillance
network has been funded by the Rockefeller Foundation,
among others. At the national level, many countries have
benefi ted from substantial fi nancial support associated
with H5N1 infl uenza, as well as HIV/AIDS, tuberculosis,
The large fl ow of foreign funding has undoubtedly
contributed to strengthening of public health capacity in
southeast Asia. But concerns have been raised. Some
observers argue that foreign investment refl ects the
interests of donor countries or mainstream trends in
public health—interests that are not necessarily aligned
with public health priorities of recipient countries.77,78 For
example, many programmes focus on high-profi le
diseases such as H5N1 infl uenza, HIV/AIDS,
Panel 3: Indonesia, virus sharing, and equitable access to vaccines
In February, 2007, amid growing international concern over the threat of pandemic
infl uenza, Indonesia’s health minister announced that her country would no longer share
avian infl uenza A H5N1 virus samples with WHO. This controversial decision was triggered
by a dispute over property rights between the Indonesian Government and an Australian
company that had used viral strains from Indonesia to produce and market an
H5N1 infl uenza vaccine. Indonesia argued that the incident exposed wider issues of
exploitation and global inequalities—pharmaceutical companies obtain, free of charge,
viral samples that are shared by developing countries with WHO, then patent the resulting
products and sell them at prohibitively expensive prices, thus providing benefi ts
disproportionately to high-income countries.68
The controversy forced WHO and its member states to reconsider the current approach to
global infl uenza surveillance and the sharing of biological materials, and to create new
mechanisms for benefi t sharing. To this aim, in May, 2007, the World Health Assembly
adopted a resolution that promoted the “transparent, fair and equitable sharing of the
benefi ts arising from the generation of information, diagnostics, medicines, vaccines and
other technologies”,68 while reasserting the need for timely sharing of both information
and biological samples with the Global Infl uenza Surveillance Network. Additionally, it
established an intergovernmental meeting to consider further actions aimed at ensuring
fair and equitable distribution of pandemic infl uenza vaccines.69
In 2008, after many debates and negotiations, the Indonesian Government agreed to share
H5N1 infl uenza sequences (but not the viral samples) through the new Global Initiative on
Sharing Avian Infl uenza Data.70 The dispute and its underlying issues, however, have not
been settled. In 2009, Indonesia did not share any samples with the Global Infl uenza
Surveillance Network, including those from pandemic infl uenza A H1N1. Moreover, the
initial eff orts to create a more equitable framework for the purchase and distribution of
vaccines have not produced any substantial results thus far. Disagreement has arisen
because high-income countries are reluctant to accept the suggestion of legally binding
obligations to share the benefi ts of vaccines that accrue from sharing of biological samples,
whereas many low-income and middle-income countries, notably Indonesia, Thailand, and
Brazil, want to see binding obligations.71
www.thelancet.com Vol 377 February 12, 2011 607
tuberculosis, and malaria, but other diseases that carry a
heavy burden of morbidity and mortality in the region
are neglected, including traditional childhood diseases,
emerging vector-borne diseases,
infections. A further concern is that disease-focused
programmes that receive substantial funding are often
poorly integrated within the wider health systems of
recipient countries. Many initiatives in southeast Asia
signify potentially important reforms—for example, the
Linked Response in Cambodia, which aims to improve
integration of vertical programmes for HIV, tuberculosis,
and maternal and child health, and the incorporation of
programmes initiated in response to H5N1 infl uenza
into the broader control programme for emerging
infectious diseases in Laos.55
Overarching many of the challenges to governance that
we have outlined is a diversity of domestic political
institutions, and tensions between and within countries
that have the potential to hamper regional eff orts to
prevent and control emerging infectious diseases.
Southeast Asia has witnessed major political upheavals
during the past decade, with military coups (in Thailand),
democratic reform (Indonesia), and a shift, albeit at
diff ering paces, from Marxism to free market economies
(Vietnam, Cambodia, Laos). Tensions also exist between
and within countries—for example, a lingering border
dispute centred on Preah Vihear temple between
Thailand and Cambodia, an ongoing ethnic separatist
insurgency in the south of Thailand, recent violence
associated with elections in the Philippines, and terrorist
attacks on tourist areas in Indonesia. The ongoing
military dictatorship in Myanmar is a continuing regional
concern. Emerging infectious diseases too have the
potential to fan the fl ames of ethnic tensions. Recently,
pigs—raised predominantly by non-Muslims in Egypt
and Malaysia, both countries with predominantly Muslim
populations—were a focus of concern regarding the
H1N1 and Nipah viruses, respectively. These political,
ethnic, and religious tensions all have the potential to
create instability that aff ects the emergence and response
to emerging infectious diseases.
Southeast Asia, a region that is home to some 600 million
people, is also the home to many driving forces of
emerging infectious diseases. The region is an
acknowledged hotspot for risk, with new, emergent, and
resurgent infectious diseases exploiting ecological niches
that result in large part from man’s infl uence on his
environment. The pace of environmental transitions that
are being witnessed in parts of southeast Asia makes the
emerging infectious disease a reality. Moreover, many of
the factors that infl uence emerging infectious diseases,
from climate change to increased global demand for
cheap protein from industrialised poultry production are
the result of powerful forces, many of which are diffi cult
to change. Southeast Asia is likely to remain a hotspot for
emerging infectious diseases, including those diseases
with pandemic potential.
The challenges that face the region therefore include
reforming or modifying of upstream driving forces of
emerging infectious diseases, prediction with improved
accuracy of where and what diseases are likely to emerge,
improvement of the governance, fi nancing, and
operational capacity of surveillance systems such that
animal and human systems are coherently and strategically
aligned, and use of timely generation of data and
information to identify feasible and appropriate responses
(panel 4). Animal and public health systems need to be
made fi t for purpose, not only to provide for domestic
needs, but also to prevent, contain, or mitigate the
emergence and spread of infectious diseases. And the
most crucial weapon in our public health armamentarium
is surveillance—a system that needs to be improved.
During the past decade, a multitude of national and
regional initiatives have developed across animal and
human health sectors in response to the threat of emerging
infectious diseases. Very substantial sums have been
invested in emerging infectious diseases in the region, in
large part in response to HIV/AIDS, tuberculosis, malaria,
and, more recently, SARS and H5N1 infl uenza. Yet the
coordination, governance, and sustainability of regional
control eff orts in the face of global economic pressures
remain a signifi cant challenge.
Panel 4: Recommendations
• There is an increasing trend towards regional coordination, cooperation, and
information sharing in southeast Asia. This trend should be complemented by a
commitment to address imbalances in health system capacity. The European Union
model for structural funds could provide a way forward.
• Emphasis on avian infl uenza A H5N1 with concomitant funding has meant the
relative neglect of lower profi le diseases such as Japanese encephalitis and rabies.
Although generic capacity building across emerging infectious diseases is to be
welcomed (for example, through the International Ministerial Conference on Animal
and Pandemic Infl uenza79) this process needs to be built on with sustained and
strategically focused funding.
• Investment in the region needs to be sustained to ensure robust, resilient, and fl exible
• Research needs to be done to improve understanding of the factors that are associated
with risk of emerging infectious diseases.
• Surveillance capacity needs to be strengthened, especially in low-income countries,
and needs to be timely, coordinated regionally, and inform national and regional
• Predictive analyses need to be strengthened, including through the development of
more robust datasets on factors associated with emerging infectious diseases such as
changes in land use.
• International and domestic governance of surveillance of animal and human
infectious diseases need to be strategically aligned across geographic, institutional,
disease, and host boundaries, and avoid duplication of eff ort
• Analyses of operational prevention, containment, and mitigation capacity are needed
to inform investment linked to global, regional, and domestic public health and
www.thelancet.com Vol 377 February 12, 2011
All authors contributed equally to the conceptualisation, literature
search, analysis, and drafting of the report.
Confl icts of interest
We declare that we have no confl icts of interest.
The paper is part of a Series funded by the China Medical Board, the
Rockefeller Foundation, and Atlantic Philanthropies.
1 WHO. Global burden of disease: 2004 update. Geneva, Switzerland:
World Health Organization, 2008.
2 Jones KE, Patel NG, Levy MA, et al. Global trends in emerging
infectious diseases. Nature 2008; 451: 990–93.
3 Woolhouse ME, Gowtage-Sequeria S. Host range and emerging and
reemerging pathogens. Emerg Infect Dis 2005; 11: 1842–47.
4 WHO. Emerging zoonoses. http://www.who.int/zoonoses/
emerging_zoonoses/en/ (accessed Nov 16, 2010).
5 WHO. Cumulative number of confi rmed human cases of avian
infl uenza A/(H5N1) reported to WHO. http://www.who.int/csr/
index.html (accessed Sept 9, 2010).
6 WHO. Pandemic (H1N1) 2009—update 58. http://www.who.int/
csr/don/2009_07_06/en/index.html (accessed Sept 9, 2010).
7 WHO. Summary of probable SARS cases with onset of illness from
1 November 2002 to 31 July 2003. http://www.who.int/csr/sars/
country/table2004_04_21/en/index.html (accessed Sept 21, 2010).
8 Lo MK, Rota PA. The emergence of Nipah virus, a highly
pathogenic paramyxovirus. J Clin Virol 2008; 43: 396–400.
9 Leo YS, Chow AL, Tan LK, Lye DC, Lin L, Ng LC. Chikungunya
outbreak, Singapore, 2008. Emerg Infect Dis 2009; 15: 836–37.
10 World Organisation for Animal Health. World Animal Health
Information Database Interface. http://www.oie.int/wahis/public.
php?page=home (accessed Nov 16, 2010).
11 UNAIDS. Report on the global AIDS epidemic. Geneva,
Switzerland: Joint United Nations Programme on HIV/AIDS, 2008.
12 Wertheim HF, Nguyen HN, Taylor W, et al. Streptococcus suis,
an important cause of adult bacterial meningitis in northern
Vietnam. PLoS One 2009; 4: e5973.
13 WHO. Multidrug and extensively drug-resistant TB (M/XDR-TB):
2010 global report on surveillance and response. Geneva,
Switzerland: World Health Organization, 2010.
14 Dondorp AM, Yeung S, White L, et al. Artemisinin resistance:
current status and scenarios for containment. Nat Rev Microbiol
2010; 8: 272–80.
15 Peiris JSM, Yuen KY, Osterhaus ADME, Stohr K. The severe acute
respiratory syndrome. N Engl J Med 2003; 349: 2431–41.
16 Li KS, Guan Y, Wang J, et al. Genesis of a highly pathogenic and
potentially pandemic H5N1 infl uenza virus in eastern Asia. Nature
2004; 430: 209–13.
17 Dry S, Leach M, eds. Epidemics: science, governance and social
justice. London, UK: Earthscan, 2010.
18 Wang H, Feng Z, Shu Y, et al. Probable limited person-to-person
transmission of highly pathogenic avian infl uenza A (H5N1) virus
in China. Lancet 2008; 371: 1427–34.
19 Ungchusak K, Auewarakul P, Dowell SF, et al. Probable
person-to-person transmission of avian infl uenza A (H5N1).
N Engl J Med 2005; 352: 333–40.
20 Global Fund to Fight AIDS Tuberculosis and Malaria. Cambodia
Round 9 Proposal Form for Malaria. 2009. http://www.
(accessed Nov 16, 2010).
21 Mackenzie JS, Gubler DJ, Petersen LR. Emerging fl aviviruses:
the spread and resurgence of Japanese encephalitis, West Nile
and dengue viruses. Nat Med 2004; 10 (12 suppl): S98–109.
22 Solomon T, Ni H, Beasley DW, Ekkelenkamp M, Cardosa MJ,
Barrett AD. Origin and evolution of Japanese encephalitis virus
in southeast Asia. J Virol 2003; 77: 3091–98.
23 Bodhidatta L, Vithayasai N, Eimpokalarp B, Pitarangsi C,
Serichantalergs O, Isenbarger DW. Bacterial enteric pathogens in
children with acute dysentery in Thailand: increasing importance
of quinolone-resistant Campylobacter.
Southeast Asian J Trop Med Public Health 2002; 33: 752–57.
24 Asian Development Bank. Assessing the impact and cost of SARS
in Developing Asia. In: Asian development outlook 2003 update.
Manila, Philippines: Asian Development Bank, 2003. http://www.
Nov 16, 2010).
25 ASEANWEB. Tourist arrivals in ASEAN. http://www.aseansec.org/
stat/Table28.pdf (accessed Sept 9, 2010).
26 Brahmbhatt M. Economic impacts of avian infl uenza propagation.
First International Conference on Avian Infl uenza in Humans;
Institut Pasteur, Paris, France; June 29, 2006.
27 Bloom E, de Wit V, Carangal-San Jose MJ. Potential economic
impact of an avian fl u pandemic on Asia. Manila, Philippines:
Asian Development Bank, 2005.
28 Murray CJL, Lopez AD, Chin B, Feehan D, Hill KH. Estimation of
potential global pandemic infl uenza mortality on the basis of vital
registry data from the 1918–20 pandemic: a quantitative analysis.
Lancet 2006; 368: 2211–18.
29 McKibben W, Sidorenko A. Global macroeconomic consequences
of pandemic infl uenza. Sydney, Australia: Lowy Institute for
International Policy, 2006.
30 Rushton J, Viscarra R, Guernebleich E, Mcleod A. Impact of avian
infl uenza outbreaks in the poultry sectors of fi ve South East Asian
countries (Cambodia, Indonesia, Lao PDR, Thailand, Viet Nam)
outbreak costs, responses and potential long term control.
Proc Nutr Soc 2005; 61: 491–541.
31 Taha FA. How highly pathogenic avian infl uenza (H5N1) has
aff ected world poultry-meat trade. Washington DC, USA: United
States Department of Agriculture, 2007.
32 UN Food and Agriculture Organization. FAOSTAT. http://faostat.
fao.org/default.aspx (accessed Sept 9, 2010).
33 Patz JA, Daszak P, Tabor GM, et al. Unhealthy landscapes:
policy recommendations on land use change and infectious
disease emergence. Environ Health Perspect 2004;
34 Coker R, Atun R, McKee M, eds. Health systems and the challenge
of communicable diseases. Buckingham, UK: Open University
35 Smith GJ, Vijaykrishna D, Bahl J, et al. Origins and evolutionary
genomics of the 2009 swine-origin H1N1 infl uenza A epidemic.
Nature 2009; 459: 1122–25.
36 Holmes EC, Twiddy SS. The origin, emergence and evolutionary
genetics of dengue virus. Infect Genet Evol 2003; 3: 19–28.
37 UN Department of Economic and Social Aff airs. World population
prospects: the 2008 revision. New York, NY, USA: United Nations,
38 Pimentel D, Cooperstein S, Randell H, et al. Ecology of increasing
diseases: population growth and environmental degradation.
Hum Ecol 2007; 35: 653–68.
39 Weiss RA, McMichael AJ. Social and environmental risk factors
in the emergence of infectious diseases. Nat Med 2004;
10 (12 suppl): S70–76.
40 Cummings DA, Iamsirithaworn S, Lessler JT, et al. The impact of
the demographic transition on dengue in Thailand: insights from
a statistical analysis and mathematical modeling. PLoS Med 2009;
41 Srivirojana N, Punpuing S. Health and mortality diff erentials among
Myanmar, Laos and Cambodian migrants in Thailand. Public Health.
91913 (accessed Nov 16, 2010).
42 Delacollette C, D’Souza C, Christophel E, et al. Malaria trends
and challenges in the Greater Mekong Subregion.
Southeast Asian J Trop Med Public Health 2009; 40: 674–91.
43 WHO SEARO, WHO WPRO. Malaria in the Greater Mekong
subregion: regional and country profi les. New Delhi, India: World
Health Organization, 2010.
44 Karesh WB, Cook RA, Bennett EL, Newcomb J. Wildlife trade
and global disease emergence. Emerg Infect Dis 2005; 11: 1000–02.
45 Erlanger TE, Weiss S, Keiser J, Utzinger J, Wiedenmayer K. Past,
present, and future of Japanese encephalitis. Emerg Infect Dis 2009;
46 Gilbert M, Xiao X, Pfeiff er DU, et al. Mapping H5N1 highly
pathogenic avian infl uenza risk in Southeast Asia.
Proc Natl Acad Sci USA 2008; 105: 4769–74.
www.thelancet.com Vol 377 February 12, 2011 609
47 Chua KB, Goh KJ, Wong KT, et al. Fatal encephalitis due to Nipah
virus among pig-farmers in Malaysia. Lancet 1999; 354: 1257–59.
48 Scoones I. Avian infl uenza: science, policy and politics. London,
UK: Earthscan, 2010.
49 Tipayamongkholgul M, Fang CT, Klinchan S, Liu CM, King CC.
Eff ects of the El Nino-southern oscillation on dengue epidemics
in Thailand, 1996–2005. BMC Public Health 2009; 9: 422.
50 Thai KT, Cazelles B, Nguyen NV, et al. Dengue dynamics in
Binh Thuan province, southern Vietnam: periodicity, synchronicity
and climate variability. PLoS Negl Trop Dis 2010; 4: e747.
51 Newton PN, Dondorp A, Green M, Mayxay M, White NJ. Counterfeit
artesunate antimalarials in southeast Asia. Lancet 2003; 362: 169.
52 Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM.
Evidence of artemisinin-resistant malaria in western Cambodia.
N Engl J Med 2008; 359: 2619–20.
53 Butler D. Disease surveillance needs a revolution. Nature 2006;
54 Narain J, Bhatia R. The challenge of communicable diseases in the
WHO south-east Asia region. Bull World Health Organ 2010; 88: 162.
55 De Sa J, Mounier-Jack S, Darapheak C, et al. Responding to
pandemic infl uenza in Cambodia and Loa PDR: challenges in
moving from strategy to operation.
Southeast Asian J Trop Med Public Health 2010; 41: 1104–15.
56 International Federation of Red Cross and Red Crescent Societies
International Disaster Response Laws Rules and Principles
Programme. Legal Preparedness for Responding to Disasters and
Communicable Disease Preparedness: study report. Kuala Lumpur,
Malaysia: International Federation of Red Cross and Red Crescent
Societies/Asian Development Bank, 2009.
57 Hanvoravongchai P, Adisasmito W, Chau PN, Conseil A, de Sa J,
Krumkamp R, et al. Pandemic infl uenza preparedness and health
systems challenges in Asia: results from rapid analyses in 6 Asian
countries. BMC Public Health 2010; 10: 322.
58 ASEAN. Regional mechanism on animal health and zoonoses
endorsed. ASEAN Secretariat, press release. May 12, 2010. http://
www.aseansec.org/24668.htm#Article-2 (accessed Nov 16, 2010).
59 WHO. Asia Pacifi c strategy for emerging diseases technical papers.
New Delhi, India: WHO Regional Offi ce for South-East Asia, 2010.
60 Putthasri W, Lertiendumrong J, Chompook P,
Tangcharoensathien V, Coker R. Capacity of Thailand to contain
an emerging infl uenza pandemic. Emerg Infect Dis 2009; 15: 423–32.
61 Adisasmito W. Health system and pandemic infl uenza
preparedness: results from a rapid situational analysis (RSA) in
Jakarta and Bali. Outbreak, Surveillance and Investigation Reports
2010; 1: 1–9.
62 Touch S, Grundy J, Hills S, et al. The rationale for integrated
childhood meningoencephalitis surveillance: a case study from
Cambodia. Bull World Health Organ 2009; 87: 320–24.
63 Mekong Basin Disease Surveillance. Action plan 2008–2013.
(accessed Nov 16, 2010).
64 Mekong Basin Disease Surveillance. Regional pandemic infl uenza
table-top exercise. http://un-infl uenza.org/fi les/asia_pacifi c/
simex/26_-_mbds.pdf (accessed Nov 16, 2010).
65 Kimball AM, Moore M, French HM, et al. Regional infectious
disease surveillance networks and their potential to facilitate
the implementation of the international health regulations.
Med Clin North Am 2008; 92: 1459–71, xii.
66 AFRIMS. Armed Forces Research Institute of Medical Sciences
(AFRIMS) Brochure. Bangkok, Thailand: Armed Forces Research
Institute of Medical Sciences, 2008.
67 Azly E. Call for closure of NAMRU-2 in Indonesia increasing.
Antara News (Jakarta), June 27, 2008. http://www.accessmylibrary.
Nov 16, 2010).
68 Fidler DP. Infl uenza virus samples, international law, and global
health diplomacy. Emerg Infect Dis 2008; 14: 88–94.
69 WHO. Pandemic infl uenza preparedness: sharing of infl uenza
viruses and access to vaccines and other benefi ts. Sixtieth World
Health Assembly Resolution. Geneva, Switzerland: World Health
70 Fedson DS. Meeting the challenge of infl uenza pandemic
preparedness in developing countries. Emerg Infect Dis 2009;
71 Fidler DP. Negotiating equitable access to infl uenza vaccines:
global health diplomacy and the controversies surrounding avian
infl uenza H5N1 and pandemic infl uenza H1N1. PLoS Med 2010;
72 Scoones I, Forster P. The international response to highly
pathogenic avian infl uenza: science, policy and politics. Brighton,
UK: STEPS Centre, 2008.
73 FAO. Livestock policies and poverty reduction in Africa, Asia and
Latin America. Pro-poor livestock polict initiative policy brief.
Rome, Italy: United Nations Food and Agriculture Organization,
74 Kanchanachitra C, Lindelow M, Johnston T, et al. Human resources
for health in southeast Asia: shortages, distributional challenges,
and international trade in health services. Lancet 2011; published
online Jan 25. DOI:10.1016/S0140-6736(10)62035-1.
75 Chongsuvivatwong V, Phua KH, Yap MT, et al. Health and
health-care systems in southeast Asia: diversity and transitions.
Lancet 2011; published online Jan 25. DOI:10.1016/S0140-
76 Krumkamp R, Kretzschmar M, Rudge JW, et al. Health service
resource needs for pandemic infl uenza in developing countries:
a linked transmission dynamics, interventions and resource
demand model. Epidemiol Infect 2010; published online Oct 5.
77 Calain P. From the fi eld side of the binoculars: a diff erent view on
global public health surveillance. Health Policy Plan 2007; 22: 13–20.
78 Shiff man J. Donor funding priorities for communicable disease
control in the developing world. Health Policy Plan 2006; 21: 411–20.
79 UN, World Bank. International fi nancial and technical assistance
report. International Ministerial Conference on Animal and
Pandemic Infl uenza; Hanoi, Vietnam; April 20–21, 2010.