Strategic Plan 2010 - 2015 - Mahidol Oxford Tropical Medicine

Transcription

The Wellcome Trust Asia MOP Network
Strategic Plan 2010 - 2015
Contents
2
Mission
4
Executive Summary
5
Objective
6
Strategic Aims
7
Background
8
Strategic Aim 1: Research
Diseases and research capabilities
Research Themes: Clinical epidemiology and diagnostics
Malaria
Dengue
Rickettsial infections, Leptospirosis and
other zoonoses
CNS infections
Tuberculosis
Influenza and other respiratory infections
Melioidosis and Staphylococcal infections
Enteric infections
Medicine quality
Strategic Aim 2: Developing People
10
12
14
16
18
20
Strategic Aim 3: Developing Institutions
36
Strategic Aim 4: Public Engagement and Outreach
38
Strategic Aim 5: Dissemination
40
Strategic Aim 6: Strengthening Governance, Management and
Financial Planning
42
Monitoring Progress
44
Current Membership of Key Committees
44
22
24
26
28
30
32
34
Strategic Plan 2010-2015
3
Mission
Targeted clinical and
public health investigation,
using the best science,
yielding appropriate and
affordable interventions to
make a significant impact
on morbidity and mortality
in the tropics.
4
Executive Summary
I
nfectious diseases remain a very real global
threat, and still account for over half the deaths
in the developing world. The Wellcome Trust Asia
Major Overseas Programmes (MOPs) conduct
medical research in the most populated area of
the world, where most of the world’s preventable
deaths occur. The region is a global hot spot for
the emergence of new infectious diseases, and it
leads the world in drug resistance. The emergence
and spread of artemisinin resistant malaria and
multi-drug resistant (MDR) TB, the scourge of
fake and substandard anti-infective drugs, and
the spectre of potentially devastating epidemics of
emerging infectious diseases all pose serious risks
for the world. In addition Asia is going through an
unprecedented period of social and environmental
change. The future impact of these changes is
difficult to predict but they will influence disease
patterns both directly and indirectly. Currently
a third of the region’s population, twice the
population of sub-Saharan Africa, lives on less
than two dollars a day. This is two-thirds of the
developing world’s poor. With a burgeoning
population and continuing high levels of poverty
in both rural and urban areas, and in the context
of a global economic downturn, the region faces
greater challenges to health than ever before.
The Wellcome Trust Asia MOP Network plans
to capitalise on our clinical and scientific research
capacity, excellent relationships with local partners,
multinational networks, and strategic geographic
position as a regional hub. Our work keeps health
research as the focus with an integrated science
programme and a particular interest in the interface
between human and animal health. Our training
and public engagement programme from schools
to post-docs and lay people is helping to build a
critical mass of Asian clinicians, scientists and the
communities in which we are based dedicated to
the development of the region and the health of its
people. The Wellcome Trust Asia MOP Network,
the product of more than 30 years sustained
investment by the Trust, is uniquely placed to
address effectively and comprehensively the
complex public health problems faced by Asia and
the world, and to make a truly significant impact
on human health both in the region and globally.
5
Objective
O
ur objective is to improve the health and
reduce the human disease burden in the
developing world. Our research focus is Asia,
as many infectious disease threats originate
in this area, but many of the principles are
globally applicable. We have shown that major
Strategic Aims
improvements in medicine can derive from a
well integrated, broad based, multidisciplinary,
multinational, clinical and laboratory research
network. We aim to inform health policy, change
practice, and reduce the mortality from diseases
in the tropics.
1
2
3
6
Research:
To conduct research into major health
problems which threaten Asia and beyond.
We will focus on a number of research
themes, chosen for their public health
importance both regionally and globally.
Developing People:
To develop a critical mass of internationally
recognised
Asian
clinicians
and
scientists dedicated to the continued
development of research capacity in the
region and the health of its people.
Developing Institutions:
To create an integrated and well coordinated
network of internationally recognised
clinical and laboratory research sites across
Asia and beyond, to deliver health advances
addressing local and global health needs.
To foster long-lasting and integrative
collaborations with local institutions
and hospitals to build both research and
administrative capacity.
4
Public Engagement & Outreach:
5
Dissemination:
6
Strengthening Governance,
Management and Financial Planning:
To engage with the communities who host
us and hence inspire and involve current and
future generations in medical research.
To provide and propagate research evidence
of the highest quality and clinical relevance,
upon which policy, both locally and globally,
can be based.
To build operational excellence through
integrated business units, enabling us to
continue realising the extraordinary research
opportunities of our Network.
7
Background
Kathmandu
T
he WT Asia Tropical Medicine Research Network (the
Network) comprises the two Wellcome Trust Major
Overseas Programmes (MOPs) and their collaborative research
sites and partners.
The Thailand/Laos MOP has a scientific and
administrative hub in Bangkok based at the Faculty of Tropical
Medicine, Mahidol University (the ‘Bangkok Unit’), and
major research units on the Thai-Burmese border (the Shoklo
Malaria Research Unit, or SMRU) and at Mahosot Hospital
in Vientiane, Laos (LOMWRU). The Bangkok Unit, its field
sites, and SMRU, comprise the Mahidol Oxford Tropical
Medicine Research Unit (MORU).
The Viet Nam MOP has its scientific and administrative
hub in Ho Chi Minh City embedded in the Hospital for
Tropical Diseases (the Oxford University Clinical Research
Unit - OUCRU). The Viet Nam Programme has major research
units in Hanoi, based at the National Institute of Health and
Epidemiology, in Jakarta, Indonesia, based at the Eijkman
Institute (EOCRU), and in Kathmandu, Nepal at the Patan
Academy of Health Sciences.
In addition to these major sites, there are a number
of study sites located across the region, including: Ubon
Ratchathani (Thailand), Chittagong (Bangladesh); Rourkela
(India), Siem Reap (Cambodia), Beijing (China) and
Rangoon (Burma). Each study site is linked to one of the
administration hubs in Bangkok or HCMC. Together the sites
form a clinical research Network across Asia. There is also a
network of collaborative research sites in Africa, conducting
the AQUAMAT study in severe childhood malaria, and in
South America through the DENCO programme on dengue.
Rourkela
Chittagong
Shantou
Hanoi
Vientiane
Rangoon
Mae Sot
Bangkok
Udon Thani
Manila
Ubon Ratchanthani
Siem Reap
Pailin
Ho Chi Minh City
Colombo
Singapore
The Network
started over thirty
years ago in
Bangkok and has
now grown from a
single research unit
in a single country
to a network across
Asia and beyond.
Jayapura
Timika
Makassar
Bandung
MOP hubs
Darwin
Network research sites
& major collaborators
Key events in the first
30 years of the Network
1979
Bangkok Unit opens;
work focuses on malaria
and snakebites.
1981
First publication –
Quinidine in falciparum
malaria, The Lancet
1986
SMRU opens; studies
in Ubon Ratchathani
(Thailand) start
1991
Viet Nam Unit
starts
2000
Laos Unit
starts
2002
Chittagong
collaboration starts
2003
Rourkela
collaboration starts
2005
AQUAMAT Network
formed in Africa
2006
Hanoi and Siem Reap
collaborations start
2007
Indonesia and Nepal
collaborations start
Strategic Aims
”We aim to conduct research into major health problems which threaten Asia.
We will focus on a number of research themes, chosen for their public health
importance both regionally and globally”.
Strategic Aim 1: Research
W
e aim to reduce the burden of infectious diseases
research plans from across the Network, and each of
locally and globally through an integrated
the two MOPs is involved in every theme. Because
approach that combines clinical and epidemiological
the research portfolios of the MOPs have evolved in
research with allied laboratory studies in a stimulating
a complementary fashion, for every theme one MOP
training environment.
has more experience and expertise than the other, so
We strive to be at the leading edge of innovation in
will take the role of ‘Theme Leader’. This will facilitate
applied clinical research, to extend our understanding
the transfer of skills and technology between MOPs
of disease and the most effective
and throughout the Network.
intervention strategies, to provide
At any one time for each theme
“...for each research
the evidence on which policy
an individual researcher will
theme, an individual
can be made and offer a vision
represent the ‘Theme Leader’
for collaborative international
MOP, and be responsible for the
researcher will represent
cooperation with a centre of gravity
coordination of research efforts
the ‘Theme Leader’ MOP,
based firmly where the problems are
across the Network.
and
be
responsible
for
the
most acute.
Scientific
strategy
and
We aim to lead the world in our
research priorities for the
coordination of research
approach in these areas. We believe
Network are coordinated by
efforts across the Network.”
that through its research activities
the WT Asia MOP Network
the WT Asia MOP Network has
Executive Committee, which
made a major contribution to regional and global
comprises the directors/senior staff of all the major
health. We have published more papers in the New
research sites, including Bangkok, Ho Chi Minh City,
England Journal of Medicine over the last five years
SMRU, Hanoi, Laos, Jakarta and Kathmandu. This
than any other single group globally and our research
meets at least once a year, and works closely with the
has played a major role in national and global policy in
MOP management/strategic committees (see figure
all our major areas of research.
on page 41). Nick White is the standing Chairman of
We retain the ability to respond flexibly to emerging
the Network, providing wise counsel and political and
threats, and through the relationships built within
scientific oversight of its activities. Chairmanship of the
host countries over decades we are trusted with the
Network Executive Committee itself rotates between
opportunity to do so.
the members on an annual basis to ensure a constant
This section addresses the research priorities across
fresh perspective on organising the Committee’s
the Network. We currently support a comprehensive
activities.
portfolio of work across a wide variety of infections and
One of the Committee Chair’s roles is to host the
our focus is on diseases that affect rural populations
WT Asia MOP Network Annual Scientific Meeting,
in Asia. The Thailand and Viet Nam Programmes
at which the latest research and operational issues from
each have foci of activity with multiple synergies
across the network are presented and discussed. This
and major overlap in the following areas; clinical
meeting provides an opportunity for scientists from
epidemiology, malaria, clinical trials, pharmacology,
across the Network to meet and share ideas, expertise,
statistics, mathematical modelling & genetics. There
and resources. It also facilitates coordination of activities
are continuous exchanges between the two research
by MOP Theme Leaders.
Programmes to ensure co-ordination and integration.
Oversight of scientific strategy is provided by the
From 2010 to 2015 all research work of the Network
two International Scientific Advisory Boards, and by
will be assigned to one of ten cross-MOP ‘research
the MOP Governing Committees and the WT Asia
themes’. Every research theme contains and unifies
MOP Network Governing Board.
10
11
Diseases and Research Capabilities
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Our research focuses on a number of diseases based on public health importance
globally and regionally. We apply our extensive research capabilities to tackling these
diseases, and have the capacity at any given time to adapt to a changing environment.
The diagram below shows a summary of our current capabilities, with the areas of
research focus highlighted by blue intersections.
Diagnostics
Drug resistance
Therapeutics/RCT’s/
Pharmacology
Immunology
Modelling/Epidemiology/
Mapping
Host and pathogen genetics
Pathogenesis/Pathophysiology
Health economics
Global networks
Effects of urbanisation and
environmental change
Advocacy
12
13
Research theme: Clinical Epidemiology and Diagnostics
Microbiology laboratories
13
involved in clinical epidemiology
studies
1
5
1
6
2
9
3
4
4
2
5
7
3
6
10
7
8
8
9
10
11
12
13
Chiang Rai
SMRU
Bangkok
Vientiane
Luang Nam Tha
Houaphan
Salavan
HCMC
Hanoi
Siem Reap Jakarta
Jayapura
Kathmandu
(Thailand)
(Laos)
(Viet Nam)
(Cambodia)
(Indonesia)
(Nepal)
12
11
Theme leader: Thailand/Laos MOP
Now
Determining the clinical epidemiology of disease
is essential for defining the research agenda most
appropriate to improve health. Infectious diseases
remain the most important medical problem in the rural
tropics. In our studies in five countries across Southeast
Asia we have found considerable heterogeneity in both
the clinical epidemiology and patterns of infectious
disease and anti-infective drug resistance. We cannot
safely generalise therefore, and so need to define and
characterise this variability to choose specific diagnostics
and empirical therapies.
The absence of laboratory facilities and point of care
tests capable of making accurate laboratory diagnoses
of a range of common infectious diseases in rural
areas, and indeed in many poor countries, perpetuates
uninformed and inappropriate empirical treatments
and contributes to millions of deaths each year from
infectious diseases in the developing world. Even
diagnosing malaria is beyond the capabilities of many
rural clinics and hospitals.
The vast majority (>90%) of diagnosis is still clinical
and syndromic, and treatment is empirical, and
resistance data very sparse.
14
Future
In the diverse rural and urban populations with
whom we work we will define the specific causes of
disease syndromes, the degree of their geographical
heterogeneity, and the patterns of antimicrobial drug
resistance.
• We will investigate the role of nutritional deficiencies
and the affect of these on infectious disease
susceptibility and outcome.
• We will use the latest technology to develop practical
tools for defining the infective clinical epidemiology
in resource-poor areas, and using the results to inform
empirical treatment regimens, the deployment of
appropriate diagnostics, clinical trials to optimise
therapy, and health policy.
• We will assess the potential public health impact
and cost-effectiveness of defining the clinical
epidemiology and its heterogeneity.
Bangkok
Melioidosis, leptospirosis, rickettsial diseases
HCMC
TB, Influenza, encephalitis, Streptococcus suis
Kathmandu
Typhoid
Siem Reap
General microbiology
SMRU
Acute respiratory infections (bacterial and viral), general microbiology
Vientiane
General microbiology, rickettsial diseases, virology
Chittagong
General microbiology, rickettsial diseases, virology
•All laboratories are considered a joint resource by
the Network, and sites with special expertise share
this with other sites as and when required, either by
transferring techniques or by shipping samples for
analysis. For example, with help from the HCMC
lab both SMRU and Laos will develop TB diagnostic
capacity to conduct epidemiological studies of TB
prevalence and the level of drug resistance. We plan
to build a new Biosafety Level 3 laboratory in SMRU
to further this aim.
• We will determine the causes of fever, especially
rickettsial, neorickettsial and viral diseases, in
urban and rural Laos, in rural Indonesia, Viet
Nam and Nepal and along the Thai-Burmese
border (EOCRU, BKK, Laos, SMRU, Cambodia,
HCMC). We will study the role of nutritional
factors (general malnutrition, B1 deficiency, noma)
in these populations.
• We will set up three new microbiology labs in
provincial Laos and conduct clinical epidemiological
studies to assess the disease heterogeneity and the
cost-effectiveness of implementing region specific
empirical treatment guidelines. We plan a new
microbiology lab in Chittagong to support studies
on typhoid and CNS infections.
• We will continue to develop and evaluate diagnostic
tests for common, treatable infectious diseases in
the region, both for use as gold standards in the
laboratory and for rapid diagnosis at the bedside.
• Mathematical modelling will be used to inform
the optimum use of diagnostics and new treatment
algorithms based on clinical epidemiological data
(BKK, HCMC).
• Geo-spatial mapping will be used as an aid to
mapping disease prevalence and to inform public
health interventions (Hanoi, Nairobi).
How
The Network has excellent clinical microbiology
laboratory facilities in a number of sites across Asia.
As well as being general microbiology labs, they have
between them nurtured considerable specific expertise
across a wide range of infectious diseases:
15
Research theme: Malaria
Clinical malaria sites
1 SMRU (Thailand)
2 Suang Phung (Thailand)
3 Bangkok (Thailand)
4 Savannakhet (Laos)
5 Pailin (Cambodia)
6 HCMC (Viet Nam)
7 Binh Phuc
Province (Viet Nam)
8 Jayapura (Indonesia)
9 Chittagong (Bangladesh)
10 Rourkella
(India)
11 Beira
(Mozambique)
12 Kinshasa (DRC)
13 Kilifi (Kenya)
14 Mbarara (Uganda)
15 Korogwe (Tanzania)
16 Muheza
(Tanzania)
17 Rwamagana
(Rwanda)
18 Nyanza (Rwanda)
19 Ilorin (Nigeria)
20 Kumasi (Ghana)
21 Bobo Dioulasso (Burkino Faso)
22 Banjul
(The Gambia)
23
10
9
1 24 7
22
3
21
20
5
6
19
12
14
17
18
8
13
1516
24
Malaria labs
23 Cambridge
(Sanger)
3 Bangkok
6 HCMC
24 Jakarta
(UK)
(Thailand)
(Viet Nam)
(Indonesia)
11
Malaria causes around one million deaths annually
and remains a huge and underestimated problem in
Asia which bears almost all the global burden of vivax
malaria, and a significant proportion of the falciparum
malaria burden.
Research carried out in both MOPs over the past 30
years has made many advances in our understanding
of the pathophysiology of malaria, and has defined the
current treatment of uncomplicated malaria, severe
malaria and malaria in pregnancy. We have pioneered
the use of artemisinin-based combination therapies
which are now first-line treatment world-wide. We have
shown that compared to quinine artesunate reduces
mortality in severe malaria in Asia. Recently we have
described for the first time the emergence of artemisinin
resistance in Western Cambodia; this is potentially the
biggest threat to malaria control worldwide.
16
•
•
How
Now
• Understand the mechanisms which control relapse
in vivax malaria, and optimise radical treatment
strategies.
• Determine the factors responsible for the emergence
and spread of antimalarial drug resistance, and
optimise methods to prevent, retard, and if possible
reverse these.
• Identify the biological, pharmacological and
molecular mechanisms underlying artemisinin
resistance in P. falciparum and find alternative
antimalarial treatment for the resistant phenotype.
• Characterise the pathology and pathophysiology
of severe and uncomplicated falciparum and vivax
malaria in adults and children, and define and
quantitate the processes in falciparum and vivax
malaria in pregnancy that reduce birthweight.
Future
We aim to improve the treatment of malaria globally.
There is renewed enthusiasm and considerable support
for malaria elimination. The focus of our work is in
Asia, which has a huge and underestimated burden of
both falciparum and vivax malaria, but our research
should improve the management of malaria throughout
the tropical world, both directly and indirectly.
Specifically, we aim to:
• Reduce the mortality and morbidity of malaria in
adults, children, and in pregnancy by optimizing
antimalarial, adjunctive and supportive treatment,
and the treatment of concomitant diseases.
• Optimise the treatment of uncomplicated vivax and
falciparum malaria in areas with high prevalences of
drug resistance, haemoglobinopathies and G6PD
deficiency.
We will coordinate and deploy the considerable malaria
expertise and scientific and clinical resources present in
both MOPs to achieve these aims. We will:
• Complete the large multicentre mortality study
comparing parenteral artesunate and quinine in
the treatment of severe malaria in African children
(AQUAMAT). Currently recruiting in 11 sites in 9
countries.
• Conduct multicentre studies of adjuvant and
supportive therapies in severe malaria, and follow
these up with appropriate multicentre studies in
severe malaria in both adult and children (Chittagong,
Rourkela, EOCRU, HCMC, AQUAMAT sites).
• Conduct studies on the pathology and
pathophysiology of both adult and paediatric severe
malaria using a variety of different approaches.
• Conduct studies on strategies to improve intensive
care treatment for severe illness including severe
malaria in hospitals in South and Southeast Asia.
• Evaluate and optimise new antimalarial combination
treatments based upon a sound pharmacokinetic
/ pharmacodynamic (PK/PD) rationale (SMRU,
•
•
•
•
BKK, HCMC). All clinical studies will include drug
measurements for correlation of drug concentration
with outcome. New methodologies to enable the
accurate measurement of drug levels from dried
blood spots will be developed to facilitate field
studies and studies in paediatric populations.
Develop PK-PD models to suggest strategies to
prevent the de-novo emergence and spread of
antimalarial resistance, the design of intermittent
preventive treatments, and drug deployment in
elimination efforts (BKK, HCMC).
Characterise
antimalarial
drug
resistance,
particularly artemisinin resistance in P. falciparum,
using clinical, in vivo, pharmacological, and
molecular techniques (genomics, transcriptomics).
Develop phenotyping and genotyping methods, and
develop and evaluate methods to prevent the spread
of these resistant parasites to the rest of the world
(Cambodia, BKK, SMRU, HCM, Laos, Sanger
Institute, NTU in Singapore). Perform clinical
trials on new antimalarials for artemisinin resistant
malaria.
Use mathematical modelling to inform the best
strategies for containing and eliminating drug
resistant malaria (BKK, HCMC).
Conduct studies in vivax malaria to understand the
pathophysiology, natural history, and population
genetics of the disease, and the role and safety
of primaquine and other antimalarials in its
radical cure (EOCRU, SMRU, HCMC, BKK,
Sanger Institute).
Develop methods for the assessment of antimalarial
drug transmission blocking activity and apply these
in field studies (EOCRU, SMRU, BKK).
Continue to conduct pathophysiological and
treatment studies of malaria in pregnancy (SMRU).
We lead the studies on the pharmacokinetics of
antimalarials in pregnancy as part of the Malaria in
Pregnancy Consortium with studies in Asia, Africa
and South America.
17
Research theme: Dengue
Theme leader: Viet Nam MOP
6
5
4
3
Dengue
research sites
2
7
9
1
8
1
10
2
3
4
5
6
7
8
9
10
HCMC
Hanoi
Bangkok
SMRU
Vientiane
Luang Nam Tha
Salavan
Attapeu
Siem Reap
Manila
• We will evaluate the diagnostic accuracy of new
rapid diagnostic tests for dengue in the field
situation. There have been many problems with the
accuracy of such tests but new assays are available
and could greatly improve the management of
undifferentiated fever.
• On a population basis we will study the interaction
between human immunity and viral genomics and
antigenicity, and use this to explore the disease
epidemiology and the antigenic evolution of
the virus.
How
Now
Dengue is the most important mosquito-borne viral
infection of humans and an enormous public health
burden in affected countries.
The Network has been at the forefront of clinical dengue
research for the last 15 years, with extensive research
carried out on the immunology, pathophysiology and
treatment of the infection. Almost all of this work
has been in Viet Nam, though research on dengue
diagnostics has been carried out in Thailand and Laos.
Research highlights include:
• The first major prospective descriptive study to
GCP standards of the clinical disease, leading to
the new WHO evidence-based clinical classification
of dengue.
• The largest ever randomised trials of fluid
management, the mainstay of treatment for shock
caused by dengue.
• First Phase II randomised RCTs of specific dengue
treatments – Chloroquine (In press), steroids
(finish 2010) and new antiviral compounds (start
Q2 2010).
• Research on better diagnostic tests for resource-poor
settings.
18
Future
• We will continue to study the ongoing Wellcome
Trust-funded cohort of children recruited at birth
(10,000 strong) to assess the early-life risk factors
for symptomatic and secondary dengue infection.
• We plan to conduct a global, multi-centre,
prospective assessment of the clinical utility of the
new evidence-based dengue classification scheme in
partnership with WHO and TDR.
• As it is unclear whether viral burden is a direct driver
of the pathophysiology of severe dengue, we will
conduct “proof of concept” clinical studies to assess
the pharmacokinetic/pharmacodynamic effects on
viraemia and clinical endpoints such as capillary
permeability.
• We will conduct Phase II clinical trials of therapeutic
interventions in severe dengue. Initial candidates
are immune-modulators, platelet infusions and
antivirals.
• We will determine the dose of contemporary dengue
virus required to infect Aedes aegypti mosquitos. This
information is important for predicting the effects
of reductions in viraemia in patients on disease
transmissibility.
The Network is in the strongest possible position to
carry out research on global health threat, with an
extensive collaborative partnership with many major
hospitals in Viet Nam as well as important children’s
hospitals in Thailand, Cambodia and Indonesia
giving access to >50,000 patients with dengue per
year. The Network has strong links with the global
dengue community through the DENCO consortium,
WHO (Chairmanship of the WHO/TDR Dengue
and Emerging Viral Diseases Reference Group),
the Paediatric Dengue Vaccine Initiative (PDVI),
and dengue genomics and drug discovery groups
in Singapore.
If, as anticipated, a candidate treatment drug
is identified, the Network will be able to use its
pharmacology and virology expertise to conduct PK/
PD studies (BKK & HCMC), and tap its own extensive
clinical resources and those of its partners to conduct
pivotal, large multi-centre Phase III studies along the
lines of the SEAQUAMAT and AQUAMAT studies in
severe malaria.
We will liaise with the National Institute of Malaria
and Entomology in Hanoi to carry out the mosquito
infectivity work.
We will use mathematical modelling to inform
the best strategies for reducing transmission through
reducing viraemia, and for controlling the spread of a
putative drug resistant virus (HCMC, BKK, Imperial).
Antigenic cartography will be carried out in collaboration
with Derek Smith’s group in Cambridge University and
Andrew Rambault of Edinburgh University, who also
work with the Network on influenza and scrub typhus
(HCMC, BKK).
19
Research theme: Rickettsial
infections, Leptospirosis and
other zoonoses
3
2
1
Clinical study sites
and laboratories
5
1
2
4 6
3
7
8
4
5
6
7
8
Now
Tropical rickettsioses, leptospirosis, and zoonoses in
general are the most under-recognised and understudied
of infectious diseases, yet they are responsible for a huge
disease burden in the developing world. This underrecognition is due to a combination of the poor and
disadvantaged nature or the afflicted populations, and
the genuine technical difficulties in diagnosing these
common infections accurately. Most bacterial zoonoses
are easily treatable, but only if the diagnosis is made,
or at least suspected, and appropriate antibiotics
administered. Lack of awareness of these diseases
leads to inappropriate empirical therapy that results in
preventable morbidity and mortality.
Over the past decade we have carried out research
to define the epidemiology, pathophysiology and
best treatment of scrub typhus, murine typhus and
leptospirosis in Southeast Asia. Highlights have
included:
• Revealing the clinical importance of scrub typhus,
leptospirosis, and murine typhus as major causes of
treatable non-malarial fever in rural Asia.
20
Bangkok
SMRU
Chiang Rai
Udon Thani
Vientiane
Savannakhet
Siem Reap
HCMC
• Development of sequence typing schemes for
leptospirosis and Orientia tsutsugamushi (the cause
of scrub typhus)
• Discovering that the recent epidemic of leptospirosis
in Thailand was caused by a single ecologically
successful virulent clone of Leptospira interrogans.
• The largest ever treatment trials in leptospirosis,
scrub typhus and murine typhus.
• Studies to understand and define the
pathophysiologies of leptospirosis and scrub and
murine typhus, including the roles of cytokines and
coagulopathy in these infections. Evidence from
pathology studies that dendritic cells rather than
endothelial cells may be the primary target cells for
O. tsutsugamushi.
The substantial work already carried out and planned
on zoonotic causes of meningitis (Streptococcus suis)
and encephalitis (e.g. Japanese encephalitis, Rabies) are
covered in the ‘CNS infection’ theme, and the work
on influenza is in the ‘Influenza and other Respiratory
Infections’ theme.
Future
As part of the Network’s commitment to the One
World One Health concept we plan to invest heavily in
this theme over the next 5 years. Specifically we plan to:
• Continue to define the epidemiology and
contribution to disease burden of rickettsial
infections, leptospirosis, fascioliasis and other
zoonoses in Southeast Asia.
• Determine whether there is significant antibiotic
resistance in rickettsial diseases in Southeast Asia,
and if so which alternative treatment regimens are
the most effective.
• Continue our investigation of the pathophysiology
of rickettsial infections, identifying for scrub typhus
and murine typhus the target cells, routes of invasion,
and seeking molecular correlates of pathogenicity.
We will work to define the human immune response
to scrub typhus and murine typhus with a view to
developing effective vaccines.
• Optimise the typing methods that are essential
for understanding the epidemiology, population
genetics, ecology and pathophysiology of these
infections. We will optimise further the MLST
typing scheme for O. tsutsugamushi, and use it to
determine the clinical epidemiology and population
genetics of scrub typhus in both patients and the
reservoir trombiculid mites. We will also develop
a novel MLST scheme for R. typhi, the cause of
murine typhus, and extend the spectrum of our
MLST scheme for Leptospira spp. to include other
pathogenic Leptospira species.
• As a global molecular epidemiological resource,
we will develop and curate the websites for all the
Programme’s schemes, in collaboration with the
curators of the mlst.net web site based at Imperial
College, London.
We will combine our spatial and molecular
epidemiological capabilities to aid the global mapping
of a number of major underdiagnosed, understudied,
zoonotic pathogens (including Leptospira spp.,
Rickettsia spp., Streptococcus suis, and Fasciola).
Working with zoologists studying the legal and
illegal animal trade in Southeast Asia we will identify
and track the epidemiology of known and unknown
zoonotic pathogens.
How
Clinical work on zoonotic diseases will be closely
integrated with the epidemiological studies outlined
in the ‘Clinical Epidemiology and Diagnostics’
Theme, and will be carried out in sites across Southeast
Asia (EOCRU, BKK, Laos, SMRU, Cambodia,
Kathmandu, HCMC). Laboratory work on culturing
the pathogens will take place principally in the
BioSafety Level 3 Laboratories in Vientiane, HCMC
and BKK. The high capacity culture facilities at the
Australian Animal Research Laboratory in Geelong,
Australia, will be used for large scale cell culture when
appropriate (collaboration with CSIRO). Molecular
and immunological work will be carried out in the
adjacent laboratories and at collaborating laboratories
in the region (Singapore (GIS), Melbourne (CSIRO)),
in Europe (Imperial College, WTSI, University of
Marseille), and in the US (UTMB, Texas).
We will work with the Wildlife Conservation Society
to sample live and dead wildlife and market workers
in wildlife markets in Viet Nam to identify known
and unknown pathogens which may cross the species
barrier and cause human disease.
The Network’s emphasis on zoonotic diseases will
be even greater in 2011 to 2016 if the Viet Nam
MOP’s Strategic Award application (WT-VIZIONS)
is successful.
21
Research theme:
CNS Infections
and laboratories
8
7
1
2
4
3
6
5
2
1
Now
Over the past 15 years the Network, led by the Viet
Nam MOP, has become a world leader in clinical
research in infections of the CNS. Highlights have
included the large clinical studies conducted on
bacterial and tuberculous meningitis (HCMC), severe
cryptococcal meningitis (HCMC, Ubon Ratchathani),
viral encephalitis (HCMC), and the aetiology of CNS
infections in Laos (Vientiane). However many questions
remain concerning the aetiology, pathophysiology and
treatment of meningitis and encephalitis.
Through the Working Group on Bacterial Meningitis
we have established a global network to develop
standard definitions and protocols for research in
infections of the CNS to facilitate multicentre studies
and allow better comparisons between studies.
Future
We plan to:
• Conduct clinical epidemiological and in depth
laboratory studies to determine the aetiology
and epidemiology of CNS infections across Asia.
The causes of bacterial meningitis vary with time,
location, age, and patient factors such as occupation
and underlying conditions. Knowing the cause in
22
3
4
5
6
7
8
HCMC
Provincial hospital
network
Vientiane
Luang Nam Tha
Siem Reap
Ubon Ratchathani
Chittagong
Kathmandu
•
•
•
a particular setting is essential if effective antibiotic
treatment is to be given. For encephalitis, even
with the best diagnostics, the underlying cause is
unknown in 70% of adults and 60% of children.
• Develop evidence-based syndromic management of
“encephalitis”. As in even the best resourced settings
it is usual for no causative pathogen to be identified,
the most fruitful approach to improving outcome is
likely to involve empirical treatment of the clinical
syndrome of encephalitis with a cocktail of antiviral,
antibacterial and immuno-modulatory drugs.
• Carry out a prospective study on the cause of hearing
loss in S. suis infections, and carry out animal studies
to assess the role of dexamethasone in preventing
this common and disabling complication.
• Conduct a clinical trial of intravenous
immunoglobulin (IVIg) for the treatment of severe
Hand, Foot and Mouth disease (HFMD). An
increase in the incidence of encephalitis in children
is thought to be due to the emergence of enterovirus
71 variants associated with HFMD and neurological
complications. IVIg has been used to treat HFMD,
but the evidence base for this is non-existent. After
in vitro assessment of the neutralizing activity of
•
IVIg from several countries a multi-centre treatment
trial will be set up.
Assess whether, in the light of the successful
treatment of a patient with bat lyssavirus infection
with amantadine and ribavirin, a treatment trial of
rabies is appropriate and ethically sound.
Conduct multicentre treatment trials to improve
the therapy of cryptococcal meningitis in both
HIV positive and negative patients. Candidate
interventions include new antifungal regimens and
adjuvant therapies such as dexamethasone.
Study the underlying pathophysiological mechanisms
of behind the link between CNS infections and
altered sodium homeostasis. Hyponatraemia is
common in both cryptococcal meningitis and TB
meningitis, and a predictor of death in the latter.
Investigate how the blood brain barrier affects
the pharmacokinetic and pharmacodynamics of
drugs used to treat CNS infections, and use this
information to improve treatment. Specifically we
shall study valacyclovir in encephalitis, antifungal
drugs in cryptococcal meningitis, and albendazole
in eosinophilic meningitis, and conduct clinical
trials of new drug regimens where appropriate.
• Investigate whether pathogen characteristics
determine the severity and outcome of CNS
infections, using a variety of approaches including
pathogen typing and population genetics, the nature
of the human immune response, and assessment of
antimicrobial drug resistance.
How
The use of multiple study sites across several countries
will provide our CNS infection studies with sufficient
power to address the above clinical and scientific
questions.
Central microbiology support and training will
be provided by HCMC, with local laboratories
providing general diagnostic support. Molecular
and immunological laboratory support will be from
HCMC, BKK, the Wellcome Trust Sanger Institute,
the University of Wageningen in the Netherlands,
China CDC and Imperial College, London.
Pharmacology support in terms of assay
development, drug measurement and PK/PD analysis
will be carried out by the pharmacology departments
and mathematical modeling groups in BKK
and HCMC.
Epidemiology
Cryptococcal meningitis
HCMC, Vientiane, Siem Reap, BKK, 14 provincial hospitals across VN,
Kathmandu, Chittagong
HCMC, Vientiane, Siem Reap, 14 provincial hospitals across VN,
Chittagong, Kathmandu
HCMC, Hanoi, Ubon Ratchathani
HFMD
HCMC, Siem Reap, 14 provincial hospitals across VN
TB meningitis
S. suis meningitis
HCMC, Hanoi
HCMC, Hanoi
Encephalitis studies
23
Research theme: Tuberculosis
and laboratories
1
2
2
3
3
HCMC
Vientiane
SMRU
•
1
Now
The Network’s TB research has until now been focused
largely on the Viet Nam MOP’s work on tuberculous
meningitis (TBM), a terrible disease which kills 25%
of HIV-ve and 60% of HIV+ve patients. Research
highlights have included:
• A large clinical trial showed that dexamethasone
increased survival in TBM, and hence changed
treatment recommendations globally.
• Further research during and subsequent to the trial
has shown that this protective effect does not appear
to be due to an attenuation of the inflammatory
immune response, is associated with decreased
matrix metaloproteinase-9 in the CSF, and may
be mediated clinically through a reduction in
hydrocephalus and cerebral infarction.
• Detailed clinical and microbiological descriptions of
the disease in the large cohort studied by the MOP.
• Identification of several host and pathogen genetic
factors affecting susceptibility to TBM.
However the mortality from TBM remains high,
particularly in HIV+ve patients (still >60%). In other
very resource-poor parts of the region the burden
of TB and the impact of drug-resistance remains
largely unknown.
24
Future
Our vision for TB research across the Network is to
build on the VN MOP’s TBM experience and develop
a wider research agenda involving continuing to
improve treatment of TBM, improving diagnostics
of TB generally, and with help from the HCMC lab
defining the incidence and improving the treatment of
drug-resistant TB in Laos and along the Thai-Burmese
border. Guided by our studies on the epidemiology of
drug resistance we plan ultimately to design and conduct
large multi-centre treatment studies of pulmonary TB.
Specifically we plan to:
• Conduct in TBM a randomised clinical trial
comparing standard anti-TB treatment with
standard treatment ‘reinforced’ by levofloxacin
(which has good CSF penetration) and high dose
rifampicin (HCMC).
• Determine whether there are significant patient
populations under-dosed on current treatment
regimens, with the attendant risks of treatment
failure and the development of drug resistance. We
will carry out PK/PD studies of HIV and anti-TB
treatment in TBM, PK studies iof anti-TB drug
levels in blood and CSF in children, further PK
studies of second-line drugs, and investigate the
•
•
•
influence of pharmacogenetic factors on the PK of
isoniazid and other anti-TB drugs (HCMC, BKK).
Conduct studies on the best methods for diagnosing
TB in Viet Nam, Nepal, Laos and Thailand. We
will develop clinical/laboratory algorithms for the
diagnosis of paediatric TB/TBM and adult TBM,
and we will conduct a clinical trial comparing
optimised MODS and the MTBDR-plus test for
the early assessment of drug sensitivity (HCMC,
SMRU, Kathmandu, Vientiane). We plan to develop
and evaluate an operating system for the diagnosis
and treatment of tuberculosis in remote inaccessible
rural areas (SMRU, Vientiane).
Determine the epidemiology of MDR and XDR TB
in Laos, and in the migrant population on both sides
of the Thai-Burmese border.
Determine whether characterization of resistance
mutations can inform treatment strategies for drug
resistant TB. Results from ongoing studies linking
drug-resistance mutations with treatment outcome
will be used to inform a clinical trial to test the
combination of rapid molecular testing for mutations
with tailored treatment regimens (HCMC).
Investigate the impact of co-morbidities on disease
progression in TBM. We will examine the impact
of Hepatitis B/C and HIV co-infections in TBM,
and how the interactions affect viral and bacterial
replication. We will also assess using sensitive deep
sequencing techniques whether resistance to ARVs
develops first in body compartments such as the
brain where ARV levels may be low (HCMC).
• Build on our findings of host genetic susceptibility
factors in TBM and conduct a multi-centre, Asiawide, genome-wide genetic association study to
identify genetic risk factors for pulmonary TB.
Functional studies will be carried out to determine
the mechanism(s) behind these associations
(HCMC, Hanoi, Thailand, Laos, Singapore).
• Determine the impact of pathogen genotype on
M. tuberculosis epidemiology using a combination
of clinical epidemiology with GIS mapping, SNP
typing and whole genome analysis (HCMC, Hanoi,
WTSI). This will be carried out primarily in Viet
Nam but will be extended to Laos and Thailand
once studies there are underway.
How
TB laboratory expertise is well developed in HCMC,
and will be shared with the new TB research sites in
SMRU and Vientiane. There is already a TB laboratory
in Mahosot Hospital in Vientiane, which has been
renovated and should be fully functional soon. We plan
to build a new TB laboratory in SMRU, which will be
an extension of the existing microbiology laboratory.
A TB treatment programme has already been initiated
in SMRU.
Given the scale of the TB problem in Laos and
Burma as expertise develops in Vientiane and SMRU
there will be enormous scope for involvement in and
contribution to multicentre studies initiated by the
VN MOP.
25
Research theme: Influenza and
other Respiratory Infections
and laboratories
1
2
2
3
4
4
3
HCMC
Hanoi
Bangkok
SMRU
1
Now
As in many resource-poor regions acute respiratory
infections (ARIs) are a major cause of morbidity and
mortality in Southeast Asia. Although pneumococcal
disease remains a major scourge, the importance of
viral infections as a common cause of severe disease is
increasingly evident. Gram-negative pathogens such as
Klebsiella pneumoniae are a frequent cause of severe
pneumonia in adults.
The Network leads the world in clinical influenza
research, and conducts research on respiratory
infections of all aetiologies. Highlights over the last five
years include:
• First detailed clinical description of H5N1 Avian
influenza in humans, and subsequent studies on the
clinical manifestations of H1N1 (2009) influenza
(HCMC, Hanoi).
• Understanding the pathophysiology of H5N1
infection, in particular the role of high viral load and
cytokine response (HCMC, Hanoi).
• Groundbreaking population level studies on the
human epidemiology of H5N1, seasonal, and
H1N1 (2009) influenza (HCMC, Hanoi).
• Advances in the pharmacology of anti-influenza
drugs, developing novel highly sensitive assays for
the neuraminidase inhibitors, and conducting
pharmacokinetic studies to assess dose regimens and
safety in both healthy volunteers and patients with
severe influenza (BKK, Hanoi, HCMC).
26
• Conducting clinical trials aimed at improving the
treatment of severe influenza (HCMC, Hanoi,
BKK, Indonesia).
• Studies of respiratory infections in a prospective
cohort of children in a refugee camp on the
Thai-Burmese border, demonstrating the clinical
importance of viral ARIs (SMRU).
For the past five years we have been at the heart
of the NIH-funded Southeast Asian Infectious
Diseases Clinical Research Network (SEAICRN),
which has funded and coordinated influenza research
and research capacity building across Asia.
Future
Across the Network we plan to:
• Develop optimal diagnostic and therapeutic
approaches to respiratory infections.
• Assess the utility of surveillance and modelling of
pathogens and populations in humans, wildlife and
farm animals for the timely detection or prediction
of emerging pathogens and the informing of public
health responses.
• Continue to characterise the causes of severe infant
respiratory infections in a rural refugee and migrant
worker population with very high infant mortality,
and determine appropriate empirical treatments
and preventive measures.
•Determine the role of urban air pollution in the
susceptibility to pulmonary infection and disease
severity, and whether the use of facemasks can
improve respiratory health.
•Investigate which host and population level factors
influence the circulation and susceptibility to avian
and seasonal influenza.
•Conduct pharmacokinetic/pharmacodynamic studies
and clinical treatment trials to assess the optimal
treatment for severe influenza infection. A study of
plasma therapy as adjuvant treatment for H5N1
influenza will be considered in China and Viet Nam.
How
We will aim to complete the existing research agenda of
SEAICRN, and will continue to use this unique clinical
research network to conduct further epidemiological
and treatment studies in influenza and other infectious
diseases (Jakarta, BKK, HCMC, Hanoi).
Expertise on the detection and characterisation
of respiratory pathogens exists in the laboratories in
HCMC and in SMRU. These two centres will work
together to optimise and harmonise methodologies for
diagnosis of respiratory infections, including RT-PCR
and point of care (PoC) tests. They are positioned close
to the clinical study sites where diagnostic utility and
the impact of test availability on appropriate antibiotic
and antiviral usage can be assessed (HCMC, SMRU).
The birth cohorts in HCMC, Dong Thap and
SMRU will continue to be followed up prospectively
to provide insight into the aetiology and frequency of
respiratory infections and the role of asymptomatic
carriage. Study protocols will be harmonised to allow
comparison between these very different settings
(SMRU, HCMC, Dong Thap).
To inform the public health response to both
seasonal and pandemic influenza and the optimal
application of interventions, the community cohort set
up in North Viet Nam will be studied to gain a detailed
understanding of the incidence and the way that
influenza is transmitted within the local community
(Hanoi). Samples from this cohort will also be used
to identify and study examples of in vivo and in vitro
heterotypic protective immunity to influenza viruses
(Hanoi, HCMC).
DNA from patients with H5N1 infection and their
relatives has been collected across the Network and in
China in collaboration with China CDC to identify
genetic risk factors for this infection using genomewide linkage and association studies The results will
inform future candidate gene and phenotype studies
(Hanoi, HCMC, BKK).
We will continue to liaise with multiple government
and non-governmental agencies in Viet Nam and
Cambodia in conducting surveillance for novel influenza
viruses in animals. We will use deep sequencing and
phenotypic prediction to predict pandemic candidate
viruses, population immune landscaping to predict
human virus evolution, and mathematical modelling
of human economic optimization and virus circulation
to determine the impact of compensation and culling
practices.
Pharmacokinetic studies will be conducted to
determine the correct dose of anti-influenza drugs in
obese individuals, in pregnancy, and in the very young,
and to assess whether there are any clinically important
drug interactions between the neuraminidase inhibitors.
Whether or not probenicid prevents the transport of
active oseltamivir into respiratory secretions will also
be assessed. In vitro PK/PD studies will investigate the
potential synergistic anti-influenza action of antivirals
in combination, with clinical trials to follow if the
results are promising (BKK, HCMC).
In a polluted setting we will investigate the effect on
health status of wearing the R95 Particulate Respirator
face mask in a 2-year community based study in which
non-smoking volunteers will be randomised to wearing
this mask.
27
Research theme: Melioidosis
and Staphylococcal infections
and laboratories
7
4
2
3
1
2
3
1
5
4
6
5
6
7
Now
Although one is a Gram negative soil saprophyte and
the other a Gram positive human coloniser, the diseases
caused by Burkholderia pseudomallei (melioidosis)
and Staphylococcus aureus have similarities in clinical
features and pathophysiology which often requires the
application of similar investigative tools. Both diseases
preferentially attack compromised hosts, both are
characterized by abscess formation and persistence, both
are notoriously difficult to treat in terms of antibiotic
resistance and the duration of antibiotic treatment
required to prevent relapse, and both are major killers.
They are both important causes of community-acquired
bacteraemia across Southeast Asia, and S. aureus is the
leading cause of hospital-acquired infections across the
world.
28
Ubon Ratchathani
Bangkok
Khon Kaen
Vientiane
Siem Reap
HCMC
Hanoi
The Thailand MOP has carried out more research
on melioidosis than any other organisation, and over
the past 20 years has conducted extensive laboratory
and clinical studies to define the pathophysiology and
optimise the diagnosis and treatment.
Staphylococcal infection is not thought of as a
tropical disease, and is consequently under-recognised
and under-studied in the resource-poor world. In fact
we have shown that the burden of disease is likely
to be as high or higher in these settings, with spread
of nosocomial infections a major clinical burden in
hospitals, and virulent clones of community-acquired
Methicillin Resistant Staphylococcus aureus (MRSA) the
cause of serious infections which are impossible to treat
with available antibiotics.
Future
Over the next five years we plan to:
• Improve the antibiotic treatment of melioidosis.
We will complete the ATOM study comparing
meropenem with ceftazidime in acute severe
melioidosis, and the MERTH study of 3 versus 2 oral
drugs in the eradication phase of treatment. We will
also conduct a population pharmacokinetic study of
co-trimoxazole in melioidosis eradication treatment,
and combine this with in-vitro drug susceptibility
data to determine the optimum drug regimen.
• Investigate potential adjunctive and supportive
treatments for melioidosis. We will conduct a
prospective study of the effect of diabetes and
glibenclamide on pro-inflammatory cytokine
and chemokine secretion in experimental and
human melioidosis. In a study of more than 1,000
melioidosis patients, we found that survival was
significantly better for diabetics taking glibenclamide
on admission compared to diabetics who were not.
We also plan to determine whether it is possible to
develop and simple, safe method to optimise glucose
control in sepsis in this setting, and whether this
improves outcome.
• Investigate whether polymorphisms affecting TLRmediated responses of the innate immune system
predispose to excessive inflammation during both
melioidosis and S. aureus infection, contributing to
poor outcomes from these infections.
• Develop evidence-based programmes for disease
prevention for both S. aureus infection and
melioidosis. A case-control study will be conducted
examining the association between activities of
daily living and risk of melioidosis, with a view to
developing simple interventions to reduce the risk
of disease acquisition. Field studies investigating
methods of environmental control of Burkholderia
pseudomallei will also continue. For Staphylococcal
infections we aim to evaluate the effectiveness and
cost-effectiveness of interventions to reduce disease
due to MRSA and other hospital pathogens, using a
combination of observational studies, mathematical
modelling, and ultimately an intervention trial.
• Conduct
preliminary
microbiological
and
immunological studies towards the development
of an effective T cell-inducing vaccine against
melioidosis.
How
Both the clinical staphylococcal and clinical melioidosis
work will centre on our permanent laboratory and
clinical study site in Sappasithiprasong Hospital in
Ubon Ratchathani, with work also being conducted in
other collaborative hospitals in Northeast Thailand, in
Siem Reap, and in Viet Nam (HCMC and Hanoi).
Melioidosis clinical trials will continue to be
conducted with the Thailand Melioidosis Clinical Trials
Group, centred in Khon Kaen University.
Microbiological and molecular work will be carried
out in BKK, and in the UK as part of our extensive
collaboration on these two diseases with the WTSI and
the University of Cambridge.
29
Research theme:
Enteric Infections
9
and laboratories
8
3
5
4
6
1
2
2
3
7
1
4
5
6
7
8
9
Now
Enteric infections contribute significantly to global
morbidity and mortality. As population growth focuses
in poor areas and one in six people do not have access
to safe water and four in ten even lack access to basic
sanitation, the morbidity from enteric diseases will
inevitably increase.
We have worked on a number of important enteric
infections, including enteric fever (typhoid and
paratyphoid – in Viet Nam, Nepal and Laos), Shigellosis
(Viet Nam) and Hepatitis E (Laos and Nepal).
For enteric fever in particular the MOPs have made
major contributions to understanding the genomics,
mechanisms of drug resistance, and pathophysiology
and treatment of the disease. Antimicrobial drug
resistance remains the biggest clinical problem in the
management of enteric fever.
Future
We plan to map the spatial epidemiology of enteric
pathogens using GIS methodologies, and use this
information combined with environmental, clinical
and pathogen genotyping data, to determine risk
factors and patterns of transmission (Dong Thap,
Nepal, Hanoi, HCMC, Sanger).
We will continue work on the pathophysiology of
enteric fever, determining using a variety of approaches
how variability in the host immune response affects
disease susceptibility (VN, Nepal and Bangladesh).
30
HCMC
Hanoi
Dong Thap
Vientiane
Luang Nam Tha
Houaphan
Salavan
Chittagong
Kathmandu
How
The laboratories in HCMC have extensive expertise
in the microbiology and immunology of enteric fever.
They will continue to share their expertise with the
laboratories in Laos and Nepal, and additionally work
with the Thai/Bangladeshi team setting up enteric fever
studies in Chittagong.
The clinical trials of fluoroquinolones and other
treatments for enteric fever will all incorporate a PK/PD
component, working with the Network pharmacology
laboratories (BKK, HCMC).
Our research on Hepatitis E will build on existing
epidemiological and clinical infrastructure in Nepal,
and existing Network experience in Bangkok and Laos.
We will continue our systematic programme aimed
at improving the treatment of enteric fever. We will
standardise trial design and ensure that antibiotic
treatment trials are adequately powered. We will
compare the new fluoroquinolones against the older
more established and failing ones, and also assess the
efficacy of cabapenems, combination therapies and
the treatment of severe disease. We will carry out in
vitro studies of time dependent killing of S. Typhi and
S. Typhi mutants by all available fluoroquinolones
(HCMC, Dong Thap, Nepal).
Antimicrobial
drug
resistance
in
the
Enterobacteriaceae is a global problem. We aim to
explore the role of the commensal flora as a reservoir for
drug resistance genes by isolating and sequencing novel
plasmids circulating within the gut flora (VN, Sanger).
We will conduct a randomised controlled multicentre
trial comparing the efficacy of ofloxacin versus
gatifloxacin for 3 days for the treatment of children
infected with Shigella spp. in Viet Nam. This study
will be conducted at HTD and Huu Nghi Hospital,
Dong Thap. Stool or rectal swab will be cultured for
Shigella and Salmonella and drug resistance testing will
be performed on all isolates.
We will investigate the role of Hepatitis E infection
in pregnancy in a large epidemiological study in Nepal,
where transmission is high and preliminary data suggests
it is a very important cause of maternal mortality.
31
Research theme: Medicine Quality
Now
Poor medicine quality is a major neglected public health
problem - a ‘mortality gap’ between clinical research
and policy making and what patients actually receive.
The Network, led by the Laos Unit, has been heavily
involved in investigating, publicising and addressing
32
this problem, particularly with regard to counterfeit
antimalarial drugs.
We are founding members of the Counterfeit
Drug Forensic Investigation Network (CODFIN)
component of the Gates ACT Consortium grant.
Future
We plan to expand our previous research to obtain
objective evidence, which is currently very sparse, on the
extent of the problem and locations of manufacturers,
and to evaluate rapid quality tests. We will use this
information in advocacy for interventions and to
build effective collaborations and data sharing between
medicine regulators, police, customs, health workers,
scientists and manufacturers.
We will continue to sample antimalarial medicine
quality in Southeast Asia and beyond, and expand
this work to other anti-infectives, especially anti-TB
therapy.
We will continue long term chemical stability
studies of antimalarial medicines in the field in Laos
and in the laboratory to obtain independent evidence
of their effective longevity and to define degradation
products so that substandard and degraded medicines
can be distinguished with more confidence.
We will evaluate and compare new Raman, NIR
and ion-mobility hand held rapid screening tools for
assessing medicine quality in outlets in Laos and Africa
(F. Fernandez, Georgia Tech and M. Green, CDC)
and assess their potential impact. If these are accurate
and easy to use they could empower drug inspectors to
make rapid, inexpensive screening chemical assessment
of medicines in the field.
How
We will build on our existing Network, our
membership of CODFIN/ACT Consortium and our
links with the wider tropical medicine community
to coordinate widespread, statistically valid sampling
in Asia and Africa and evaluate sampling techniques
and interpretation of forensic data with INTERPOL/
IMPACT.
We will continue close collaboration with the
laboratories of F. Fernandez (Georgia Tech), D.
Mildenhall (GNS), and M. Green & S. Smith (CDC)
on the development and assessment in the field and in
the laboratory of innovative new chemical and biological
forensic techniques to understand the epidemiology
and source of poor-quality medicines.
Our hope is that this work will help advocate change
globally, so that this essential but neglected component
of effective medical care is given the attention it needs.
33
Strategic Aim 2: Developing People
“To develop a critical mass of internationally recognised Asian clinicians and
scientists dedicated to the continued development of research capacity in the
region and the health of its people”.
Now
The present capacity to initiate and lead health sciences
research in Asia is limited, and as a consequence the
health research agenda largely continues to be set and
driven by external agencies and institutions to an
unacceptable degree.
Many factors contribute to this lack of capacity,
including:
• A paucity of established research programmes and
networks with a sufficient critical mass of high quality
researchers; a lack of appropriate career structures
• A failure by some agencies to recognise that capacity
building and strengthening need to be long term and
conducted on a substantial scale. In particular there is a
lack of emphasis on postdoctoral research support and
many Asian researchers find themselves without support
and often with inappropriate levels of administrative
and teaching responsibilities. This in turn means that
individuals cannot develop the necessary research
experience to allow them to compete internationally
for funding or credibly mentor the next generation
of research trainees. A further great impediment to
research, in some countries where the MOPs work,
is the paucity of scientific and technical staff able to
perform the laboratory and QA fundamental work
essential for research.
The WT Asia MOPs Network has over the years
recognised the deficit and worked hard to mitigate it in
the context of our research programmes. This has been
either ad hoc, by for example employing and training
research assistants on fellowships and projects, or as
part of the Training Programmes that the two MOPs
have initiated and developed over the past decade.
Both MOPs are have met the stringent standards
to become UK Open University Affiliated Research
Centres (ARCs), through which we can register and
supervise Open University MSc and PhD students. We
also supervise BSc, MSc and PhD students through
Mahidol and Oxford Universities and the University
of Natural Sciences HCMC. We have developed
34
a core PhD didactic training course held one afternoon
a week and lasting for one year and available for all
PhD students registered through the MOPs. This is
coordinated through the HCMC and BKK MOPs but
is available on line and via video link in real time to all
satellite centres with PhD students. Attendance will be
mandatory for all PhD students from 2011. We believe
this to be a unique programme and seeks to ensure
that all PhD students across our Network have basic
knowledge and skills across the range of disciplines
required by a modern post-doctoral scientist including
science, administration, management, presentation
skills, grant and manuscript writing.
The MOP training programmes have begun to bear
fruit. From 2005 to 2010 students in the two MOPs
have successfully completed and been awarded 35 BScs,
31 MScs and 52 PhDs. Many of these PhD students
have gone onto to post-doctoral positions within
national institutions, universities or hospitals, have
secured international funding or taken posts in major
international universities, or have gone on to work
within the private sector.
• To build leadership capacity by supporting
senior researchers to develop their publication,
training, teaching, strategic management and
mentoring skills.
• To help build well trained, experienced, highly
motivated clinical research teams that can
contribute to the development of both institutional
as well as national clinical research capacity
through the training and involvement of medical,
nurses, scientists, pharmacists, technicians, data
management and related staff in all aspects of
clinical trials and allied laboratory science.
• We aim to specifically champion training and
regional capacity enhancement in the areas
of translational research, public health and
health systems research, epidemiology, clinical
trials, mathematical modelling and health
economics, bioinformatics, biotechnology and
public engagement.
How
Our expanded training and capacity development
strategy will be based on the existing MOP-based
training programmes, in enhanced and integrated
forms. These will continue to facilitate MSc and PhDbased training, but will also focus on more practical
skills-based training aimed at increasing the quality
of health care provision and research participation.
This latter category is important everywhere but of
particular relevance in more resource-poor regions
in the Network where the baseline skills base is low.
It will consist of vocational scientific, administration,
management, grant and manuscript writing, clinical
and laboratory training, short courses, and language
training. The two Clinical Trials Units will carry out
training on all aspects of clinical research, including
ICH-GCP compliance and ethics.
We will develop a combined Network-wide
approach to resource further training and capacity
building. This will be coordinated by the Network
Executive Committee and will consist of:
• Better coordination of the activities of the two
MOP Training Committees.
• Development of dedicated training facilites in
HCMC, Hanoi, Bangkok, Jakarta and Vientiane.
• Network-wide fora for students to meet and
exchange ideas and experiences, through the annual
Network meeting, discipline-specific gatherings and
video-conferencing.
• Joint applications for funding, including our planned
application for a Strategic Award for Training in 2011
which will focus on the development of middle and
senior career research leaders through a dedicated
collaborative WT-Asia Leadership Programme.
Future
We want to build on the success of the current training
programmes, expanding their scope and capabilities to
achieve the following strategic training aims:
• To provide a coherent career development track for
health researchers across Asia.
• To target key areas of health related research that
needs particular strengthening in Asia: Public
Health, Clinical Research, Bioinformatics and
Mathematics, Biotechnology, and Translational
Research.
• To strengthen regional research capacity through
supporting outstanding individuals linked to the
Wellcome Trust Asia MOP Network and through
developing networks with universities and research
centres within the region.
35
Strategic Aim 3: Developing Institutions
“To create an integrated and well coordinated network of internationally
recognised clinical and laboratory research sites across Asia and beyond, to deliver
health advances addressing local and global health needs. To foster long-lasting
and integrative collaborations with regional institutions and hospitals to build both
research and operational capacity”.
Now
Over the past three decades the research offices, labs
and clinical facilities of the WT Asia Research Network
have evolved in symbiotic manner with the institutions
which host us. These institutions vary enormously
across the region, from University Faculties through
large regional referral and provincial hospital, smaller
district hospitals, small health clinics right down to
isolated refugee camps with no prior health system. In
every setting we aim to ensure that working with the
Network strengthens the institution, that we put in
much more than we take out.
In Bangkok, the Faculty of Tropical Medicine of
Mahidol University in which we are embedded is world
renowned for its research output - it is celebrating its
50th anniversary this year - an achievement we have
been proud to have contributed to both directly and
indirectly over the years. At the same time the support
and contribution of the Faculty has been critical for the
success of the MOP’s success. Through the collaboration
with the MOP the Faculty has international standard
malaria, microbiology and pharmacology laboratories,
all manned by staff who are also academic members of
the Faculty.
Because of its isolation and the areas where it works
the development of the health care and research facilities
at SMRU have been a particular achievement, one
which has depended on the dedication of the staff and
the population which they serve, as well as the support
of the local Thai health services and of the Faculty of
Tropical Medicine in Bangkok.
In Viet Nam we have received fantastic support
over the last 18 years from the Hospital for Tropical
Diseases and the Ministry of Health. In the spirit of
true collaboration the Institute of Clinical Sciences
which houses the Unit was built with funds from the
Vietnamese government as a long term investment
in research excellence, and much of equipment and
running costs are provided largely by the MOP. HTD
is currently building new wards which will include the
first dedicated facility in Viet Nam for the care of people
36
living with HIV with space for outreach, counselling,
education and training and a second block for the
investigation of patients. We have been fully engaged
in the development of these new facilities and will be
actively involved in work in them. In Hanoi the offices
of the network are hosted both by the National Institute
of Tropical and Infectious Diseases and the National
Institute of Hygiene and Epidemiology. The WT Asia
MOP Network has refurbished the newly established
National Office of Health Research within the Ministry
of Health Viet Nam and the Department of Health
HCMC. These offices serve as the coordinating centre
for all health related research in Viet Nam including the
administrative support for the independent National
Health Ethics Committee.
All our main collaborative sites across the region
have dedicated clinical research units, laboratories and
office space now established at the various hospitals
and institutes where we work. A prime example is in
Mahosot Hospital in Laos, where we have worked
closely with the Hospital authorities to complete a new
building which houses the Hospital’s Infectious Diseases
Ward on the ground floor and the research unit’s offices
and laboratories (including a BSL3 laboratory) on the
floor above. In Kathmandu the clinical research unit is
a department of the newly established medical school
Patan Academy of Health Sciences dedicated to the
training of clinicians, nurses and midwives who will
work in rural Nepal.
Future
Over the next 5 years we aim to continue to develop and
strengthen the research units and facilities which make
up the Network, and the institutions which host them.
Our vision is to construct an Asia wide international
Network dedicated to clinical and public health
research, embedded within national institutions but
with sufficient scale to enable the network to conduct
the large scale intervention studies needed to provide
the evidence in which to change policy and practice.
• We will continue to strengthen ties with the Faculty
of Tropical Medicine Mahidol University and the
wider University. We aim to integrate completely
the Thailand components of the Programme,
with our Thai staff employed as University staff.
In conjunction with the Faculty we will set up a
‘Dean’s Research Fund’, via funding from Oxford
University. This fund will support enhanced career
opportunities for Thai staff, through structured
fellowships and research project funding.
• Our partnership with HTD in HCMC will continue
to be the bedrock of the Viet Nam MOP, supported
by the Department of Health Ho Chi Minh City
and the Vietnamese government. The partnerships
with Children’s Hospital Number One, Number
Two, Pham Ngoc Thach TB Hospital in HCMC,
Dong Thap Hospital and at the National Hospital
for Paediatrics, National Institute of Hygiene
and Epidemiology, and the National Institute for
Tropical and Infectious Diseases in Hanoi will be
the basis for a wider plan to greatly expand the
institutional research capacity of Viet Nam through
the Ministry of Health in the coming years. We hope
to expand the Clinical Science Institute (addition of
an extra floor) in HCMC to gain additional space
for academic meetings (now open to all hospitals,
institutions and Universities in HCMC), and
training courses and workshops. The later includes
open days for schools, universities and the general
public to allow them to see research in practice.
• We shall develop and support the clinical services
provided by SMRU to the Burmese migrant and
refugee communities on the Thai-Burmese border,
by raising service-related external grants. This is
imperative from a humanitarian viewpoint, but also
constitutes an essential underpinning of SMRU’s
research activities. In support of the research we
hope to build a BSLIII laboratory at SMRU, to
expand our clinical and diagnostics services beyond
the focus on malaria. The research activity in turn
informs the best-possible health care for these
populations, and provides an important evidence
base for the treatment of similar diseases in other
poorly resourced rural communities. These activities
on the border are appreciated and endorsed by the
Thai Ministry of Public Health.
• We will continue to work closely with Lao colleagues
at Mahosot Hospital in Vientiane, to build research
capacity and to support the infection-related
clinical and laboratory services. We will support
the refurbishment of the hospital microbiology
department to upgrade the facilities to international
standards. We will facilitate the development of
future Lao leaders in infectious disease research
through formal training and participation in
the Network.
• We will support the development of clinical and
laboratory research capacity across the Network
and specifically in Bangladesh (Chittagong),
Nepal, Cambodia (Siem Reap and CNM in
Pnomh Penh) and Indonesia. We will do this by
training of individuals in laboratory techniques
and formulation of research ideas and projects.
Also we hope to support a Category III laboratory
in Chittagong.
• We will build on the excellent safety culture cultivated
and strengthened throughout the Programme,
and optimise robust biosafety and biosecurity
systems for managing Category 3 organisms and
‘select agents’.
• We plan to improve the level of intensive care
medicine in developing countries in Asia by
developing a structural training programme in
intensive care medicine for developing countries
in Asia, including Bangladesh, India and Nepal.
We will implement essential but low cost clinical
management techniques and introduce tools for
measuring performance.
How
To achieve this we will work closely with all our partners
in the region, and with our stakeholders in the UK.
We will:
• Foster the strong institutional backing, excellent
administrative support, and increasing recognition
of tropical medicine in Oxford University.
• Continue the process of strengthening the financial,
grants administration and research governance
across the Network, integrating the policies and
administrative processes of its geographically
disparate constituent parts.
• Increase the size of the Finance Departments and
recruit staff members to act as liaisons between hubs
and different research sites across the Network.
Also, we aim to introduce new finance systems to
improve our capacity for financial management
and reporting.
• Work with Oxford University, the Wellcome Trust
and other funders to seek and develop funding
opportunities and strategies to help build research
institutions across Asia.
• Leverage the power of international research
networks, working with new and existing networks
to achieve our research and institutional capacitybuilding aims.
37
Strategic Aim 4: Public Engagement and Outreach
“To engage with the communities who host us and hence inspire and
involve current and future generations in medical research”.
Now
Over the next five years and beyond the WT Asia MOP
Network is committed to developing and expanding
our Programme of Public Engagement with Science.
We recognise the importance of this initiative, and
the challenges associated with engaging populations
in the developing world. Across Asia countries vary
greatly in the baseline level of education and exposure
to scientific ideas, due to a combination of cultural
and political factors as well as the overall level of
economic development.
Our Programme of Public Engagement with Science
(PES) is most developed in the Viet Nam MOP, where
it is run by a full time Public Engagement Officer.
The PES programme is initially focused in three areas:
media, science cafes and in schools.
We plan to expand the PES Programme to Thailand,
where for cultural reasons the opportunities and
challenges will be quite different to those in Viet Nam.
There is at present relatively little public engagement
of medical research in Laos, with relatively low access
to newspapers and TV. Much of the population
is very isolated and very poor, making PES a
significant challenge.
Of more direct interactive relevance to the clinical
research we carry out is the concept of community
engagement in research through outreach to the
communities with which we work. The Network
conducts a lot of research in vulnerable populations,
including poor disadvantaged communities, ethnic
minority refugee and border/migrant populations.
We are aware that this complex environment presents
unique challenges including ethical, practical and
scientific challenges.
We have long been engaging the community through
38
informal consultation with community leaders, key
workers, local hospital staff and regulatory authorities
but have not formalised these initiatives until recently.
SMRU has been involved in providing healthcare
and conducting research in the Thai-Burmese border
population (consisting of Karen and Burmese refugees
and migrants) have recently facilitated the formation of
the Tak Province Border Community Ethics Advisory
Board (T-CAB) with support from the Ethox Centre in
Oxford. The aim of the T-CAB is two fold - to safeguard
the rights, safety and wellbeing of research participants;
and to enable stakeholders from the border population
to have an opportunity to learn about, understand the
need for, and participate in medical research undertaken
in their community.
• Encouraging the Wellcome Trust Museum to
undertake a “Road Trip” to Asia in the next
few years.
• Working through Universities and Science institutes
to learn about their research and encourage
dissemination with the public.
• Establishing a nationwide, annual competition for
science reporters based on the best science story of
the year.
• Writing science news and stories which prioritize
local science activities.
• Organize a club for science reporters and writers
which would meet monthly. The purpose of the
club would be to provide an opportunity to meet
and exchange experiences on science writing, study
English and discuss with scientists about issues
in science.
• Establishing a Science Cafe as a meeting place
where people can come together and talk about
science. The objective is to provide an easy way for
individuals and groups to become more engaged
with the subject. This is turn could have an influence
on the educational route they decide to follow, and
the career they choose to pursue.
• Choosing a suitable school to build a small centre
like the Unizul Science Centre in South Africa
with a variety of science activities (science shows,
science theatre – hot topic such as HIV/AIDS, avian
influenza - and competition between the schools).
• Launching a science research programme for
school students.
The above plans will be adapted and implemented in
other parts of the Network as appropriate. In Laos
for example we plan to write Lao language newspaper
articles and information sheets in Lao for patients on
the major infectious diseases of Laos, to help with the
naming, in Lao, of recently described diseases in Laos,
and continue to help with the setting up of the ‘Lao
Medical Journal’ which is the first medical journal in
Laos since the 1930s.
For our Community Outreach Programme we
envisage that through the experience of facilitating the
set up of the T-CAB in SMRU, similar community
advisory boards will be formed in other communities
the Network work in and with.
Future plans
We will expand and develop the Public Engagement
with Science Programme across the Network. We
plan to apply for further funding from the Wellcome
Trust Engaging Science grants programme to provide
resources for this expansion.
The PES Programme has initially focused in three
areas: media, science cafes and in schools. Plans already
initiated or planned include:
• Plays focused on health research and conducted in
schools (see attached)
• Information access to the major newspapers have
dedicated science pages.
• A training course for science reporters to equip them
with science writing skills that can engage the public
(our first dedicated science journalist will complete
his Masters Degree in Bristol in 2010 and return to
the Network).
39
Strategic Aim 5: Dissemination
“We aim to provide and propagate research evidence of the highest quality and
clinical relevance, upon which policy, both locally and globally, can be based”.
T
o follow our mission and achieve our principal
objective of “improving the health and reducing
the human disease burden in the developing world”,
we need our research findings to make an impact
on health policy and ultimately clinical practice.
We aim to achieve this through a number of related
mechanisms:
• Timely publication of our research results in high
impact journals. Over the past 5 years we have
published over 900 original articles and reviews. We
aim for full compliance with the Wellcome Trust’s
Open Access policy, to ensure that the papers are
feely accessible by all.
• Presentations of salient research findings at national
and international conferences.
• Membership of WHO Committees and other
national and international bodies advising on
treatment guidelines and health policy issues.
• Giving interviews to the press, both scientific and
general, on recent research advances and their
public health implications.
• Through up-to-date, informative, attractive and
easily navigable websites describing the latest
research news and providing access and links to
results and guidelines. Where appropriate we will
distribute this content in alternative user-friendly
40
formats such as the Mahosot Microbiology Review,
a Lao and English language newsletter distributed to
all hospitals across the country.
• Making datasets and research materials rapidly and
freely available on-line when possible for other
researchers to work on.
• We aim to be the first organisation to make all
study protocols, CRFs, SOPs, and all study
documents available online through a Wiki
mechanism at the start of studies. This aims to ensure
that the concept of sharing of data is extended to the
initial phase of research (ie study design, protocols,
CRFs, consent sheets, study manual of operations
etc) and one which is increasingly becoming such
a handicap to researchers in the developing world.
When appropriate these will be translated into other
languages such as with recent work with pandemic
influenza (www.seaicrn.org) and malaria (www.
wwarn.org).
• All data is produced and shared in adherence
to the principles of the Wellcome Trust Data
Management and Sharing Policy, the University
of Oxford Clinical Trials & Research Governance
data management policy and section 5.5 of the
International Conference for Harmonisation Good
Clinical Practice guidelines.
Skin biopsy of an eschar lesion from a patient
with scrub typhus. Specific staining was
performed with a double-immunofluorescence
technique, demonstrating the superficial
dermal vascular plexus in red (targeting CD31
receptors) and the bacteria causing disease
Orientia tsutsugamushi in green. This picture
shows an Orientia-infected cell transmigrating
through the endothelial monolayer of a blood
vessel in the skin. Large picture, magnification
x400, insert Laser Scanning Microscope image,
magnification x1000.
41
Strategic Aim 6: Strengthening Governance, Management and
Financial Planning
“To build operational excellence through integrated business units, enabling us
to continue realising the extraordinary research opportunities of our Network”.
T
he Network has grown organically over the last
30 years, and will continue to evolve over the
coming 5 years. We will continue to develop our
management and governance structures to help us
achieve our five-year strategic aims efficiently, cost
effectively, and with minimum institutional risk.
Independent Scientific Advisory Boards (ISABs)
Governance: external oversight and
challenge
Management: internal oversight and
challenge
We will ensure an appropriate governance structure
is always in place to support and guide the Network,
enabling us to achieve our strategic aims with maximum
efficiency and impact while minimising institutional
risk.
We recognise the need for high level oversight of
the Network and for the Directors and other senior
researchers to be challenged on the strategic direction of
the mission. Our governance structure, which includes
external oversight (in blue in the organigram) consists
of three major components:
Our internal management structure (in red in the
organigram) is designed to be efficient and flexible
and the key aim is to facilitate and encourage the
identification and rapid response to the public
health crises and extraordinary research opportunities
which regularly present themselves in the field
of tropical medicine research. The Network has been
able to respond quickly to past public health
emergencies in Asia; this is our core capability,
and one which we intend to protect and build on in the
next five years.
WT Asia MOP Network Governing Board (to
be constituted)
The WT Asia MOP Network Executive
Committee
The new over-arching Governing Board will provide
the top level of governance for the Network. It will have
representatives from the two MOPs, the University
of Oxford and the Wellcome Trust, as well as several
independent and lay members. This Board will provide
external oversight and challenge for all of the Network’s
activities.
MOP Governing Committees
These two committees meet annually and govern
the activities of the MOPs in their principal host
countries, and provide legitimacy for their local role.
The Thailand/Laos MOP Governing Committee has
representation from Mahidol University, the Wellcome
Trust and Oxford University. The OUCRU Governing
Committee has legal status in Viet Nam as the governing
body presiding over OUCRU in its status as an NGO
under Vietnamese law.
42
Each MOP has an ISAB which meets roughly every
18 months. Their remit is to provide independent
scientific advice to the Programme regarding research
activities. They report to the Senior Investigators, to
Oxford University and to the Wellcome Trust.
Made up of the Network’s lead researchers this committee
binds the Network together at the level of executive
direction, strategic planning and operational activities.
It is in constant session by email and teleconference
addressing problems, exploiting synergies and planning
the Network’s response to new research opportunities as
they arise. The Committee will meet in person at least
once a year, with the chairmanship of this committee
rotating on an annual basis between the Network’s
Research Directors.
The MOP Management Committee structure
Each MOP has a small number of committees devoted
to the running of the Programme and its associated
research network. As well as overseeing operational and
financial management, they will also review research
plans on a regular basis and ensure that funding follows
excellence in research. Within the Thailand/Laos
MOP the Finance Committee addresses and monitors
budgetary and fundraising issues, financial control and
financial related risk, the Science Committee decides
on MOP scientific priorities and allocates science
funding, and Management Committee oversees general
operational issues. In the Viet Nam MOP The Strategic
Committee decides on scientific priorities and makes
high level budgetary decisions, while the Finance
and Operations Committee and Department Heads
Committee cover financial and general operational
issues
Research ‘Theme leaders’
For each Theme a senior investigator will ensure that the
Network’s plans in that research area are as integrated
as possible, exploiting the many synergies between the
sites in terms of human capacity, research facilities, and
access to affected populations for clinical studies.
Financial planning
We aim to avoid any shortfalls in funding that may
impede the efficient functioning of the Network and
impair the realisation of our research aims. We will
achieve this through analysis of our funding gaps and
the development of a fundraising strategy.
A pre-requisite for good financial planning is
the accurate collection (preferably automated) and
analysis of detailed financial information from each
business unit. Our existing IT arrangements with
functional accounting systems, but without embedded
management information systems (MIS), mean that
data collection and analysis is modest and reasonably
manual. Over the period of this strategic plan each
MOP will have a financial planning group tasked to
upgrade its accounting and MIS system capabilities
with a view to enabling efficient and accurate collection
of data to make feasible analysis and production of
detailed projections of future use, as well as reports on
how efficiently funds have been spent in the past.
The Resource Mobilisation Officer (or fundraiser)
will produce a fundraising strategy with a horizon of
5 years or more in the future. This financial planning
and fundraising capability will be fully integrated into
the risk management strategy of the Network; any
shortfalls in funding will be predicted in ample time for
corrective action to be taken.
WT Asia MOP Network
Governing Board
Thailand/Laos MOP
Governing Committee
Thailand/
Laos ISAB
OUCRU Governing
Committee
external
oversight
Viet Nam
ISAB
Local
partners
Local
partners
Thailand/Laos
MOP Management
Committee
WT Asia MOP Network
Executive Committee
internal
oversight
Finance
Committee
Science
Committee
Viet Nam MOP
Strategic
Committee
Finance & operations
Committee
Department Heads
Committee
WT Asia MOP Network Research Units, Departments and Research Sites
Figure. Governance and management committee structure for the WT Asia MOP Network. Strategic Plan 2010-2015
43
Monitoring Progress
Strategic Committee
– OUCRU Viet Nam
Over the course of the period covered by this Strategic Plan we will use a robust approach to measuring progress
against our aims, and this will help us inform future strategy. Consideration will be given to measuring progress at
the Network, MOP and also country levels. Evaluation will ensure accountability and responsibility for funding
decisions and ensure that money continues to follow good science. Initially we will use high level indicators of
progress, as outlined below, although we recognise that these may change over the course of the five year period.
Aims
Research
Developing People
Developing Institutions
Public Engagement,
Outreach Dissemination
Management and
Governance
Indicators of Progress
• Key contributions to the evidence base for improved prevention,
treatment and diagnosis of infectious diseases
• Continued grant funding in support of our mission
• Frequent publications in internationally recognised and high impact journals
• Development of a cadre of internationally recognised, local
scientists and clinicians
• Provision of an internationally competitive career path for local
scientists and clinicians
• Development of well equipped - world class - research laboratories
and study sites
• Development of strong and long-lasting links between local
institutions and hospitals
• Uptake of research into policy and practice
• Continued extension of research activities to health service
provision
• Continued support from local stakeholders
• Implementation of best practice in financial and management
systems, both internally and locally
Current Membership of Key Committees
As at 1st August 2010
Professor Nick Day
Director of Thailand/Laos Programme
Dr Arjen Dondorp
Deputy Director of Thailand/Laos Programme
Professor Jeremy Farrar
Director of Viet Nam Programme
(OUCRU VN)
Professor Tran Tinh Hien
Vice Director of OUCRU-VN and Director of
Clinical Research
44
Professor Tran Tinh Hien
Vice Director of OUCRU-VN
and Director of Clinical Research
Dr Peter Horby
Vice Director of OUCRU- VN
and Director of OUCRU-Ha Noi
Dr Niklas Lindegardh
Head of Pharmacology
Dr Daniel Paris (Acting)
Head of Microbiology
Ms Kanchana Pongsaswat (Phung)
Office Manager
Dr Laura Merson
Head of Clinical Trials Unit
Professor Sasithon Pukrittayakamee (Yon)
Deputy Dean for International Relations
and Networking
Dr Cameron Simmons
Mrs Mondira Sarapak (Ting)
Chief Financial Officer
Dr Bridget Wills
Associate Professor Pratap Singhasivanon
Dean of the Faculty of Tropical Medicine
Sarah Barton
Head of Operations
Dr Lisa White
Head of Modelling
Management Committee
– Thailand/Laos Programme
Professor Nick Day
Director of Thailand/Laos Programme
Professor Nick White
Principle Research Fellow
Mrs Vanaporn Wuthiekanun (Lek)
Laboratory Representative
Dr Ruth Branston
Senior Research Administrator
WT MOP Network Executive Committee
Dr Kevin Baird
Director of OUCRU-Indonesia
Professor Jeremy Farrar
Director of Viet Nam Programme (OUCRU-VN)
Professor François Nosten
Director of SMRU
Dr Peter Horby
Vice Director of OUCRU-VN and
Director of OUCRU-Ha Noi
Dr Paul Newton
Director of LOMWRU
Professor François Nosten
Director of SMRU
Professor Nick White
Chairman of WT Asia MOP Network
Chief Operating Officers - Thailand and Viet Nam
Dr Phaik Yeong Cheah
Head of Clinical Trials Support Group
Dr Kesinee Chotivanich (Nok)
Head of Laboratory Malaria
Dr Arjen Dondorp
Deputy Director of Thailand/Laos Programme
Mr David Gandy
Fundraiser
Mrs Sawanya Ismael (Aeh)
PA to Programme Director
Dr Paul Newton
Director of LOMWRU
45
Wellcome
Trust
Asian Asian
Wellcome
Trust
Southeast
MOP
MOPNetwork
Network
Design: Joss Dimock

Strategic Plan 2010 - 2015 - Mahidol Oxford Tropical Medicine

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