Memorandum by Research Councils UK
Research Councils UK is a strategic partnership
set up to champion the research supported by the seven UK Research
Councils. RCUK was established in 2002 to enable the Councils
to work together more effectively to enhance the overall impact
and effectiveness of their research, training and innovation activities,
contributing to the delivery of the Government's objectives for
science and innovation. Further details are available at www.rcuk.ac.uk
This evidence is submitted by RCUK on behalf
of the five Research Councils listed below and represents their
independent views. It does not include or necessarily reflect
the views of the Science and Innovation Group in the Department
for Innovation, Universities and Skills. In addition to contributing
to the main text, four of the Councils have provided additional
specific information about their research in separate Annexes,
as detailed below:
Biotechnology and Biological Sciences Research
Council (BBSRC) Annex 3
Economic and Social Research Council (ESRC) Annex
4
Medical Research Council (MRC) Annex 5
Natural Environment Research Council (NERC)
Science and Technology Facilities Council (STFC) Annex
6
Annex 1 explains the abbreviations used in the text,
and Annex 2 provides examples of Research Council contributions
to the work of Intergovernmental Organisations.
INTRODUCTION
1. The Research Councils welcome the opportunity
to respond to the House of Lords Committee's Call for evidence.
2. In this introduction, we aim to set relevant
activities of the UK Research Councils in the broader context
of the role of science and international community in addressing
the challenges of health and disease globally. The scope of many
questions asked in the Call is broad, reflecting the interconnectedness
of science, organisation and policy, and of research and downstream
development and implementation to improve health. Within the limitations
of Call specification, we are not able to address all questions
comprehensively, for instance in relation to Questions 2 and 6.
3. The protection of populations from infectious
diseases is of concern to international organisations, particularly
UN organisations such as the WHO, not least because of the rapidity
of spread from one country to another (as instanced by SARS) and
the potential scale of human mortality (eg 1918 pandemic influenza)
and socioeconomic impact of endemic disease (eg HIV/AIDS, malaria,
high worm burdens). Furthermore, the social and economic impact
of infectious disease in Low Income Countries (LICs) poses threats
to global security.[32]
(Annex 1 provides a glossary of abbreviations).
Global Health Research
4. The Research Councils' investment in
research relevant to health of the world's poorest people and
disadvantaged populations ("global health") is significant,
both in terms of scale and sustained commitment. The outcomes
of our research, often executed with or subsequently built on
by partner organisations, has had a significant impact on international
health policies, particularly through the World Health Organisation
(Some examples are provided in Annex 2).
5. Funding research in and involving LMICs
is not only consistent with the principle of international solidarity
(as espoused in the UN Millennium Goals and by the Africa Commission),
but also benefits the UK. In particular, the UK can learn from
the clinical experience where infections are more prevalent than
in the UK and—through partnerships with the governments,
organisations and communities of those countries—conduct
research not possible in the UK. The host countries benefit from
the translation of the knowledge gained into new and improved
policy, practice and products, investment in health and research
infrastructure, and the development of human capital. Intergovernmental
organisations, such as the World Health Organisation (WHO), play
an important role in promoting implementation of research findings.
6. From a broader perspective, research
itself is an international activity that is actively promoted
by the Research Councils. The Committee should be aware that several
international research organisations that do not fall directly
within the scope of the Call enable essential basic science, for
instance the European Bioinformatics Institute (a component of
the European Molecular Biology Laboratory).
The Global Burden of Infectious Disease
"Infectious diseases in humans now threaten
us all—and with our assistance, can cross the globe in hours.
Worldwide, they account for over a fifth of human deaths and a
quarter of morbidity. They disproportionately affect the poor—in
some African countries, they have contributed to reducing life
expectancy to around 40 years".
Foresight.[33]
7. The global burden of infectious disease
is unevenly distributed. Data for 2002 indicated that 75% of all
deaths due to infectious disease occurred in southeast Asia and
sub-Saharan Africa.[34]
Emerging economies typically experience a shift as new wealth
brings changes in diet and lifestyle. These changes then become
reflected in a steep rise in non-communicable diseases, such as
cardiovascular disease, cancer and diabetes. Working with national
governments, and organisations such as the US Centres for Disease
Control and Prevention (CDC) and its EU equivalent (ECDC), the
WHO has leading normative role in monitoring and reporting these
trends and promoting appropriate public health responses.
An Historical Perspective
8. The 20th century saw many campaigns to
control or eradicate particular "the great" endemic
infectious diseases, in particular:
— malaria (many regional successes
in control where the epidemiology of the disease, transmission
characteristics and sustained country resources were compatible
with success; in sub Saharan Africa the approaches were not compatible
with any sustained impact);
— polio (eradication prevented by pockets
of entrenched population rejection of immunisation and subsequent
spread);
— onchocerciasis (successful control
in large parts of west Africa); and
— the elimination in China of filariasis
by sustained chemotherapy in some 350 million people.
9. That these campaigns were "vertical"
(specific to one disease) often reflects the unique biology of
each of the pathogens (involving, for many, intermediate vectors
such as the mosquito). Consequently, each control programme demanded
a specialism in surveillance and control technologies and skills.
Many were launched at a time when the military had a prominent
role in tropical infection control and when colonial infrastructures
were in place. Success or failure depended on many factors—biological,
social, economic and organisational. Common to the history of
the great campaigns is their scale, systematic and disciplined
organisation, cost and challenges of sustainability. Each also
had to be tailored to the specifics of the disease epidemiology,
the biology of pathogen, human and vector, and behavioural, social
and environmental influences—ie a strong basic and translational
research base.
10. Today too, one strategy cannot fit all.
So, HIV, MRSA, TB and influenza prevention each require an infection-specific
set of behavioural responses by people as individuals, as well
as differentiated interventions at organisational and societal
levels. Inevitably, the current state of knowledge and the tools
available for control differ from one infectious disease to another.
Categories of Infectious Disease
11. In considering the effectiveness of
the international response to infections, the following three
categories of infectious disease, based on endemicity and availability
of effective strategies for population protection, may be of use
to the Committee:
— Endemic diseases for which effective,
cost-effective interventions are available: Diseases caused
by worms exact a significant burden on people's ability to work
and resist other infections. They include filariasis, onchocerciasis,
Guinea worm, schistosomiasis and intestinal worms that cause anaemia.
Low cost or donated drugs that are effective in reducing new cases
(incidence) and in improving health. For each parasite, research
has shown low cost drugs to be effective in reducing new cases
(incidence) and in improving health. For instance, river blindness
(onchocerciasis) is no longer a public health problem for some
60 million people in 10 West Africa countries, as a result of
community distribution of donated ivermectin (Mectizan, Merck
& Co. Inc), effected through the African Programme for Onchocerciasis
Control (APOC) across 19 countries. However, other such opportunities
(eg for community control filariasis, viral hepatitis and respiratory
and diarrhoeal disease) remain unrealised: neglected, according
to some commentators, by the international community's concentration
on the big three (HIV, TB and malaria)—excluding the majority
of the worlds poorest from cost-effective programmes that would
have a rapid impact on people's lives.
— Endemic disease for which affordable,
effective interventions are not (or incompletely) available:
HIV, malaria and TB are endemic in much of the developing world
and in Africa in particular. Each is difficult to prevent or treat,
and has sophisticated biological mechanisms for persisting in
its human host, serving also as a continuing reservoir of new
infection. For malaria, there are some 13 candidate drugs in clinical
trials. Combination therapies and insecticide-treated bednets
may now be turning the tide in malaria control. But they will
need implementation tide on a vast scale: even then transmission
is unlikely to be completely halted. 16 malaria vaccine candidates
are in clinical trials, one of which is expected to reach Phase
3 clinical trials shortly.[35]
For HIV, a vaccine is more distant goal, requiring long term investment
in basic and translational research. Current antiretroviral therapies
(ART) are based on combination therapies that keep the virus in
check but people remain infected and may experience ill health
as they age with HIV. The development of technologies languishes
for neglected diseases characterised by a relatively low prevalence
(eg African trypanosomiasis, sleeping sickness).
— Emergent potentially epidemic
infections for which interventions may not be effective or available:
Newly emergent viruses with exotic names often excite considerable
attention, although their global burden is usually infinitesimal.
Vigilance and coordinated, rapid response are essential because
viruses against which human populations have had no prior exposure,
and consequently no acquired immunity, have caused epidemics in
the past (eg 1918 pandemic influenza). Adaptation to man of viruses
whose natural hosts are birds or other animals, and to easy transmission
from one person to another, is difficult to predict. In the case
of avian flu, such viruses seem likely to emerge from South Asia
where high human population density, close contact with food animals,
poor husbandry and high humidity occur on a large scale. Current
technologies cannot yet deliver an effective pandemic flu vaccine
to populations in advance of an outbreak. Moreover, the arsenal
of effective drugs is small.
Intergovernmental Organisations and Research
12. International (including intergovernmental)
organisations have a crucial roles in research that are
additional to coordinating international health controls. Their
roles include the following:
— Promoting alignment of translational
research strategies to internationally agreed public health priorities.
— Informing international health policy
development on the basis of research evidence.
— Standardisation in research (eg IAVI's
role in reagents, research protocols, and measures of effect in
HIV research).
— Catalysing collaboration between
the best research teams internationally, including collaborative
access to research infrastructure (eg well equipped, skilled laboratories
"at the front") and resources (eg well defined study
cohorts in populations of relative high prevalence, samples and
data).
— Stimulating the development of research
(and control) capacity in endemic (often low income) countries.
Examples include programmes of the European and Developing Countries
Clinical Trials Partnership (EDCTP) and the UNICEF/UNDP/World
Bank/WHO Special Programme for Research & Development in Tropical
Diseases (TDR).
13. A range of organisations are active
internationally. They can be characterised as follows:
— International governmental organisations
(IGOs): Foremost in health is the WHO. Other United Nation
organisations that have acquired health mandates include UNICEF,
The World Bank, UNDP UNAIDS, the World Food Programme and UNFPA.
A similar set of organisations are active in the control of animal
disease including the OIE (and there are important issues about
the connectivity between the two sectors), especially as three-quarters
of human pathogens are derived from animals. There are perennial
concerns about competition or duplication within the UN family
and need to coordinate veterinary and human public health agendas
in the zoonoses.
— National governmental organisations
with an international mandate: These include the UK Department
for International Development (with which MRC, ESRC and The Wellcome
Trust all have partnership programmes), and the USA Centres for
Disease Control (the UK's Health Protection Agency does not have
an equivalent international mandate).
— International non-governmental
organisations and foundations: Foremost among the NGOs funding
and influencing research are the large private foundations, the
Bill and Melinda Gates Foundation (Gates Foundation) and, in biomedical
research, The Wellcome Trust. Many international (and national)
NGOs whose primary remit is the delivery of healthcare also play
a crucial role in engaging communities (and countries) in health
and social research, eg in clinical trials and studies of health
behaviours.
— Public private partnerships:
Over a 100 PPPs are contributing to the development of new drugs
and vaccines for infectious disease. These can be separated broadly
into (a) product development partnerships such as the MMV or DNDI
and (b) Alliances and partnerships committed to delivery of interventions
for particular diseases or conditions. These partnerships have
emerged for a variety of reasons, including limited confidence
in WHO to deliver on its mandate and the need to involve NGOs
as implementers.
— International financing mechanisms:
The Global Fund for AIDS, TB and Malaria (Global Fund), the US
President's Emergency Plan for AIDS Relief (PEPFAR) and the President's
Initiative in Malaria (PMI) are directing significant new funding
into infectious disease control. There is concern in the research
community over the power of these organisations (and the Gates
Foundation) to drive the disease control and research agenda (their
funds dwarf those of the WHO). Criticisms include: too great a
focus on vertical programmes and "the big three" diseases;
too great an optimism based on a narrow set of strategies and
technologies, for which evidence of public health impact is often
inadequate; too little consideration of distortion of recipient
country policies and health systems.
14. The relationship between the Research
Councils and international governmental and non-governmental organisations
is as follows:
— A RC role in representing the UK,
eg the MRC role in the EDCTP, IARC (a WHO organisation) and the
EMBL, among others.
— RC-funded scientists (at UK universities
and RC institutes in the UK and overseas) act as technical advisors,
eg to WHO and Gates Foundation—informing research strategy
and evaluating research proposals and progress.
— RC-funded scientists and staff lead
and coordinate research programmes that these organisations coordinate
and/or fund
— The funding of major Research Facilities
eg Diamond by the Wellcome Trust.
15. A combination of technical advice and
research, eg the role of the MRC National Institute of Medical
Research WHO Influenza Centre in identifying new flu strains and
informing WHO policy on the strains to be included annually in
seasonal flu vaccine.
16. It is important to recognise that international
governmental organisations, typically those of the UN and European
Union, are only part of the picture, there are many other actors
such as academia and the Non Governmental Organisations, many
of which work together with IGOs through specific partnerships
(eg StopTB).
RESPONSES TO
SPECIFIC QUESTIONS
17. In the remainder of the RCUK submission,
our response follows the Committee questions, which are reproduced
in italics.
1. A recent report on Communicable Diseases
by the UK Department of Health[36]
stated that "post-war optimism that their conquest was near
has proved dramatically unfounded". What is your assessment
of the overall position? More specifically, is it simply that
not enough progress is being made in reducing the spread of such
diseases? Or is the global situation actually deteriorating? Would
it be an exaggeration to talk of a crisis?
"While there is great uncertainty about
the future, we should expect many of today's major human and animal
infectious diseases to broadly continue in importance—indeed,
it could be decades before some, like HIV, will peak. However,
we should also expect diverse diseases to continue to emerge or
re-emerge. Infectious diseases will continue to jump between wild
and domesticated animal species and humans".[37]
Foresight.
18. Getting Ahead of the Curve[38]
rightly highlights the challenges of controlling endemic infectious
disease and outbreaks caused by newly emerged, re-emerged or newly
resistant infectious agents. Knowledge about the epidemiology,
the biology, social and environmental determinants of transmission,
infection and disease; the tools for diagnosis, prevention and
treatment; the systems for innovation and implementation; and
the research evidence of what works—are all essential to
realistic disease prevention and control targets and strategies.
19. In relation to the UK, the optimism
seems unfounded, not only in relation to the health and economic
consequences of important human infectious diseases (MRSA, STDs)
but also the even bigger economic losses related to infectious
diseases of animals with (eg BSE) and without (eg foot and mouth)
spread to humans.
20. The progress globally in the last 20
years in reducing morbidity and mortality from many infectious
diseases is demonstrated by the dramatic reductions in infant
and child mortality, especially post-neonatal mortality, which
in these age groups was mainly of infectious causes. Vertical
control programmes have achieved significant progress in several
tropical diseases particularly in Asia and the Americas. Sub-Saharan
Africa has seen success in vertical onchocerciasis and trachomatitis
control, but still lags behind on key Millennium Development Goal
(MDG) targets. However, vertical programmes can challenge already
fragile health systems (eg salaries of polio surveillance officers
being >10-fold that of doctors in other parts of the health
sector in sub-Saharan Africa).
21. On the positive side, the perception
that poverty related diseases would be eliminated as a consequence
of economic development has been replaced by appreciation of a
two-way process in which disease control is itself a driver for
development, leading to an increase in awareness and funding for
disease control efforts.
22. There are still opportunities to implement
affordable, simple, and effective interventions, such as de-worming
in LMIC settings, that could bring significant benefits not only
to health but, for instance, success in education. That they are
not is considered by some commentators to be a failure of policy
and political will. They argue that by harnessing funding streams
to the big three, other more achievable health gains are being
neglected. Not surprisingly, others highlight the entrenched challenges
and burdens attributable to HIV, malaria and TB in particular,
and the need for concerted, sustained and focused funding and
action.
23. Challenges to the global community include
the scale and speed of individual travel and population movement,
greater exposures to zoonotic infections, complex social, economic
and environmental changes (eg lifestyle, land and water use, livestock
practices, urbanisation, trade and economic conditions, climate
and the distribution of vectors of disease) and fragile health
systems. For many populations, the threat from exotic infection
and the burden of endemic infectious disease can be expected to
become worse—possibly much worse. From the perspective of
2008, sub-Saharan Africa looks to be particularly, though not
uniquely, vulnerable.
2. What reliable data exist regarding the
numbers of people infected globally with the four diseases[39]
on which the Committee is focusing particular attention? What
trends are discernible in both the numbers infected and the patterns
of infection? And what are the main underlying causes of infection
and of any changes in its incidence and pattern?
24. The WHO puts a huge effort into developing
reliable estimates of mortality, morbidity, health burden etc.
The scale of mortality is 1.7 million deaths annually due to TB;
1 million due to malaria and 2 million due to HIV. These estimates
are based on models that draw on relatively few studies, which
themselves may have had limitations. The estimate of avian flu
deaths (some 200+) is also a likely underestimate, due to weak
surveillance and reporting systems.
25. UNAIDS recently revised downwards its
estimate of the prevalence of AIDS to 33.2 million,[40]
partly as a result of improved methods for in-country data collection
and analysis and reflecting revisions of estimates in India. While
the prevalence may be levelling off, new infections and longer
survival mean that the number of people living with AIDS is still
increasing. Two-thirds of people with HIV live in sub-Saharan
Africa. Experts are concerned that in this region in particular,
the patchy roll-out of antiretroviral therapy (ART) in weak health
systems, together with the debilitating effects of co-infection
(with TB and with other sexually transmitted diseases, STDs),
will create circumstances that favour the emergence of drug-resistant
strains of virus. Possible adverse effects of ART availability
on preventative behaviours, such as condom use, are another major
concern.
26. In the case of malaria, mis-diagnosis
of clinical cases averages some 60% and can be as high as 90%.
The main reasons are symptom overlap with bacteraemias and pneumonias
and mis-classification of causes of death (any child dying with
a history of fever in the malaria season likely to be labelled
a malaria death). These are significant challenges to data reliability.
The lack of autopsies and accurate post-mortem pathology means
that the accuracy is unlikely to improve and WHO will continue
to rely on models to extrapolate from the limited surveillance
data.
27. Nevertheless, there are encouraging
signs that malaria is decreasing in some parts of Africa, possibly
through some increased access of poor people to effective treatments
(including the new combination therapies) and insecticide-treated
bednets (ITNs). However, these measures leave behind a non-immune
population of susceptible individuals, so sustained surveillance,
application of preventative measures and the availability of effective
and affordable drugs is essential.
28. The Bill & Melinda Gates Foundation
has recently committed itself to eradicating malaria in the longer
term. Some experts are sceptical that this achievable. They consider
there remains an urgent need for more accurate and earlier diagnosis,
new antimalarials and the development of an effective vaccine
to ensure that such success can be maintained.
29. TB data are weak because, like malaria,
accurate diagnosis is challenging. Particularly worrying are multi-
and extensively drug resistance (MDR and XDR, respectively) strains,
and strains not recognised by routine diagnosis and surveillance.
Globally, the number of people infected with TB is likely to rise
owing to resistant strains and co-infection with HIV. Furthermore,
the only vaccine for TB (ie BCG) is ineffective against the major
form of the disease; no new drugs have been developed for TB since
the 1960s.
30. As at 11 January 2008, the WHO reported
the cumulative number of laboratory-confirmed human cases of avian
influenza A/H5N1 as 349, including 216 deaths. It is likely that
these data underestimate the actual number of cases because reporting
systems are weak in many of the countries concerned (see our response
to Question 3). The panzootic in birds continues (expanded during
2005 to encompass Europe and Africa as well as Asia); occasional
human cases continue to be identified in new locations emphasizing
the continued pandemic threat.
31. Experience has shown that the overall
burden of infectious diseases decreases as economic status improves.
This process is now taking place in the newly developing economies
in Asia where non-infectious diseases are overtaking infections
as the main cause of ill health. However, in sub-Saharan Africa
infectious diseases still account for a high proportion of deaths
and serious illnesses, especially among children.
32. As indicated elsewhere in our response,
the underlying causes of infection and changes in prevalence and
threat are infection-specific and often complex. There is an extensive
research literature that it would be inappropriate to try and
review here.
3. What intergovernmental surveillance systems
exist to give early warning of outbreaks of infectious diseases?
Are these systems adequate? And what improvements might be made?
33. Surveillance networks abound but are
fragmented, mostly formed along political rather than geographic
lines. For instance, WHO regions reflect political expediency
(with India and Pakistan, north and South Korea, and Israel and
Palestine in separate regions). The European Centre for Disease
Prevention & Control (ECDC) comprises only EU countries, excluding
big non-EU countries such as Turkey through which infections may
pass. In the WHO/Afro Region, meetings are held along language
lines not geography. Sudan is included in the Eastern Mediterranean
Region and not the Afro Region. Despite efforts, eg of the WHO
Health Metrics Network, laws, procedures and practices for health
data sharing remain inconsistent between countries.
34. Commentators consider the numerous surveillance
and control activities of WHO, CDC, ECDC, and national public
health authorities to be fragmented and patchy, with gaps in coordination
and continuity. Vertical disease-specific programmes are perceived
as operating independently of each other, even within the same
organisation. There are concerns about duplication of effort and
lack of sustainability. Although focusing on pandemic threats,
the 2005 International Health Regulations (IHR) could provide
a basis on which to build comprehensive surveillance, including
the legal framework for countries to improve and share surveillance
data.
35. There is need to develop and sustain
laboratory capacity in developing countries across the spectrum
of infectious disease surveillance. Past donor initiatives have
lacked continuity. While building capacity, the accountability
required of vertical programmes has in some cases actively hindered
broader microbiological capacity development. There is a challenge
for IGOs—and WHO in particular—to facilitate, foster
and fund systems that develop and sustain epidemiological and
laboratory capacity, so that surveillance and response can be
effective—and cost-effective—across a range of infections.
36. Surveillance and modelling of social,
environmental (including climate) and biological changes (including
in animal host and vector populations) likely to be associated
with new or increased transmission could be coordinated to improve
timely preparation and response measures.
37. The extensive 2005 Foresight[41]
project on the detection, identification and monitoring of infectious
disease identified the importance of the following in surveillance:
simple, affordable, non-invasive near-subject testing; high throughput
detection systems (eg for screening at airports); and novel information
systems rapidly to capture, analyse and interpret diverse, high-volume
data. Implementation of such technologies will depend on internationally
agreed policies and standards.
4. Given the continuance of current or planned
intergovernmental programmes to prevent or control the four diseases,
what predictions can be made of their likely spread and pattern
over the next 10 years?
38. Sub-Saharan Africa in particular has
a significant challenge to reach the health-related MDGs.[42]
Experts comment that even where the tools are available, political
commitment is often lacking and health systems fragile. To provide
quantitative predictions is difficult for the reasons given in
our response to Question 3.
39. The research community is more optimistic
about malaria control than about TB, and TB than HIV. This reflects
the availability and implementation of effective tools for reducing
transmission of infection and for treating those people already
infected, as discussed earlier in this submission. Over the past
ten years there has been remarkable progress in developing drugs
for AIDS patients and significant progress in distributing them
in resource-poor countries. However these treatments are not curative
and the development of vaccines and microbicides capable of preventing
HIV-1 spread has been disappointingly slow. HIV/AIDS will therefore
continue acting as a major brake on global development for the
foreseeable future.
40. Even were the MDG targets of placing
more people on ART achieved (eg "3x5" HIV treatment
target, with around 1.2 million people on ART in Africa in 2006),
this alone would not achieve a reduction in HIV transmission.
41. Drug resistance has persistently bedevilled
malaria and TB control. Combination therapies, eg in HIV and malaria,
may reduce the likelihood and rate of spread of resistant strains,
but rigorous monitoring is required to contain emergent strains.
That in turn requires strengthening of in-country laboratory capacity.
42. Resistance is emerging in Anopheles
mosquitoes to the pyrethroids that are the active insecticides
in ITNs. The efficacy of bednets cannot be expected to be retained
for much more than a decade without the need to a new insecticide.
Most public health pesticides were first developed for agriculture.
Research on new insecticides effectively ceased as the agrochemical
industry turned to genetically engineering crops that are intrinsically
resistant to pests.
43. Surveillance and control of infections
other than the big three must be sustained, eg in measles, which
could rebound and again cause more deaths than malaria.
44. The Lords' Committee will be aware of
expert opinion that an influenza pandemic is inevitable but unpredictable—given
gaps in fundamental understanding of the natural distribution
of flu viruses in bird populations, the adaptation of avian (and
other potentially other) flu viruses to rapid human-to-human transmission
and the causes of human death and survival when infected.
5. What do you consider to be the principal
blockages to achieving progress in the prevention or control of
the four diseases? And how might these blockages be removed by
more, or better-targeted or better-coordinated intergovernmental
action?
45. The list of barriers to progress cited
by the research community is long:
— A critical technical issue is the
accuracy and timeliness of diagnosis. Late diagnosis often equates
to "too late for treatment" (and this applies equally
to non-communicable disease). Untreated infections can also fuel
ongoing transmission.
— Treatment and prevention strategies
rely on a small number of tools, many with limited or waning effectives
(BCG vaccine, and drugs) and important gaps (eg absence of vaccines
for malaria and HIV).
— Failures of international and national
policy makers to commit to action where knowledge and tools are
available. Similarly, the understandable focus on LICs may divert
action and funding from MICs, where transmission control may both
be more tractable and provide models and skills transferable to
LICs.
— Failures within and among international
organisations, including IGOs, to coordinate and sustain surveillance
and control activities. This applies to animal diseases (eg avian
flu in poultry) as well as to human infections.
— Credibility of international organisations
that set unrealistic targets, eg the Roll Back Malaria Abuja targets
for net coverage, 3x5 for HIV treatment (See paragraph 40).
— Inadequate knowledge of the (often
complex) biology of infection, disease and transmission; the contribution
of behaviour/lifestyle; and of more distal environmental factors
necessary for the design of effective surveillance and control
strategies. As the Call recognises, objectives can be overly optimistic,
not least because policies are inadequately based on robust evidence.
— Weak health, higher education and
innovation systems for translating knowledge and technologies
into policy and practice.
— Finite capacity of LMICs to absorb
advice, not least because those "who need to know" are
overwhelmed by (a) operational obligations, (b) the number, complexity
and sometimes rivalry of donors, and (c) a plethora of policies
and guidance.
— The relatively low commercial rewards
for developing new products for low income populations.
— Cultural and political resistance
to effective prevention strategies, such as condoms (by some donors)
and vaccines (by some populations) and, in developed markets,
the potential for litigation.
— Inconsistent laws, policies and practices
(and uncertainties about interpretation) eg in datasharing and
the distribution of intellectual property rewards.
— Weak health education at community
levels, particularly of women.
— Conflict and insecurity.
— Weak governance in many LICs both
at a national and institutional levels. Distortion of priorities
resulting from an imbalance of power and resources.
6. What role does your organisation play in
combating the four diseases? Do you believe that it is correctly
configured and adequately resourced to do the job? With which
other organisations do you collaborate? How would you assess the
degree of synergy?
BBSRC
46. BBSRC funds research on animal diseases,
of which work on zoonoses has relevance to this Inquiry. This
includes studies of the pathogenesis of viral, bacterial, parasitic
and fungal infections of animals, including host/organism interactions
at the cellular and molecular levels. The Council encourages the
development of novel approaches to the control of new and emerging
diseases as well as alternatives to existing chemotherapeutics.
BBSRC also funds research on arthropod vectors of animal pathogens
that might provide models for understanding the incidence and
spread of malaria or other vector-borne human diseases. However,
BBSRC does not fund research focused on specific human diseases
and disease processes, which fall within the remit of the Medical
Research Council.
47. Of particular relevance to the present
inquiry, in 2007, BBSRC funded four awards, totalling £4.5
million, under its Combating Avian Influenza Initiative. Further
details of this initiative are provided in Annex 3.
48. Additionally, in 2006-07, BBSRC spent
the following estimated sums on research relating to malaria (£1,338k,
including work on mosquitoes), avian influenza (£842k), HIV/AIDS
(£186k) and human (non-bovine) tuberculosis (£930k).
ESRC
49. The ESRC funds research on population
dynamics and social factors in relation to health and has two
key research schemes relevant to this enquiry:
— a responsive-mode scheme in partnership
with DFID; and
— a collaboration with the Hewlett
Foundation to examine the relationship between population and
poverty with a focus on a range of reproductive health issues.
50. ESRC has funded several HIV and TB relevant
projects through the two schemes (there are no projects specifically
on malaria). ESRC funding on these diseases is mainly made in
response to proposals from academia. Responding to public health
needs for interdisciplinary research in on influenza, ESRC recently
coordinated the development and funding of the project, Behavioural
Responses to Pandemic Influenza (PI) in the UK. Further details
of the ESRC portfolio are at Annex 4.
MRC
51. The MRC expenditure on global infections
research in 2006-07 was £30.4 million. By disease, the investment
was as follows:
— Infections £30.4 million, of
which: £10.9 million on HIV/AIDS; £7.8 million Malaria;
£7.1 million Bacterial infections including TB; and £4.6
million other infections (including helminth, bacterial, protozoa,
non-HIV viruses.
The distribution of that expenditure was as
follows:
— £11 million—intramurally
in Africa through the MRC Gambia Laboratories (working on malaria,
TB, HIV and other virus infections) and the MRC/UVRI Uganda Research
Unit on AIDS.
— £8 million—intramural
programmes at NIMR and UK-based MRC Units (including the MRC Human
Immunology Unit).
— £12 million through grants and
fellowships in UK Universities, including support for the MRC
Tropical Epidemiology Group at the London School of Hygiene and
Tropical Medicine (LSHTM).
52. In addition, Council has made the special
contributions of £1.2 million in 2006-07 as co-funding of
trials and capacity building with the EDCTP (see below) and £2
million in 2005-06 to strengthen clinical trials capacity at the
Tanzanian National Institute for Medical Research in Mwanza, underpinning
LSHTM programmes funded by the MRC. Examples of MRC programmes
are at Annex 5.
53. The MRC benefits from several strategic
partnerships in global health research, including the following:
— Department for International Development
(DfID): DfID funding to MRC of £4 million per annum underpins
basic and translational research immediately relevant to DfID's
health strategy. In addition, £9.25 million of MRC funding
for three large trials HIV studies is matched by £45 million
of DfID funding.
— European and Developing Countries
Clinical Trials Partnership (EDCTP): The EDCTP is a partnership
between 16 European countries and 46 sub-Saharan African countries
with funding from the EU and the European partners. In developing
new clinical tools against AIDS, malaria and tuberculosis the
EDCTP coordinates and funds Phase II and III clinical trials in
Africa and associated research capacity development.
— The UK Funders Forum for Global
Health Research brings together the MRC, The Wellcome Trust,
ESRC and DfID. The Forum identifies opportunities for closer coordination
and joint working.
— The UK Collaborative for Development
Sciences (UKCDS) see paragraph 60.
NERC
54. The Centre for Ecology and Hydrology
(CEH), one of the Research Centres wholly owned by NERC, has conducted
extensive research into the molecular biology of human pathogens
and their modes of action. It is now focussing more on the environmental
distribution and transport of certain pathogens, the ecology of
selected invertebrate vectors and the distribution and role of
pathogens in the population biology of natural (non-human, non-livestock)
hosts in the environment.
55. It is worth noting the significant effect
that some diseases can have on wildlife populations and ecosystem
function—with implications for humans. An obvious example
is the impact of squirrel pox on the balance between red and grey
squirrel populations. The potential for climate change to cause
habitat loss and crop and tree damage through effects on the spread
of pathogens is particularly concerning.
56. The recently-announced "Living
With Environmental Change" (LWEC) interdisciplinary policy
partnership programme, being led by NERC, will help to improve
our understanding of climate change and the prediction of local
and regional change, which should help to provide the basis for
improved prediction of the spread of vectors and pathogens. NERC's
Environment and Human Health programme and the Ecosystems Services
for Poverty Alleviation (ESPA) programme will both contribute
to LWEC.
57. NERC-CEH is keen to work with researchers
funded by other relevant Research Councils such as BBSRC and MRC
where possible in the area of emerging diseases, and cross-Council
programmes such as LWEC provide one opportunity.
7. What are the main non-health causes (eg
global warming, poverty, changes in land use, international travel,
lifestyle, population) of the spread of the four diseases? To
what extent can intergovernmental action in non-health fields
contribute to alleviation of their spread? What action is taking
place or planned in these areas? And what more needs to be done?
Do you consider that there is sufficient "joined-up"
thinking in approaching the problem?
58. Several of non-health issues are identified
elsewhere in our response, in particular under Question 5.
59. Taking a developing country perspective,
a range of other infectious diseases are significant causes of
morbidity and mortality in the developing world. Many are water
borne and food-borne infections. It is important to tackle their
underlying socioeconomic and environmental causes. This again
argues for a health systems approach embedded in a strong public
health policies that aims for multiple disease containment and
prevention.
60. The newly established UK Collaborative
for Development Sciences (UKCDS) brings together several RCs (BBSRC,
ESRC, MRC, and NERC), DfID and other government departments. It
is currently examining opportunities for cooperation and synergy
in climate change and research capacity development. Prompted
both by this initiative and the NERC's Environment and Human Health
programme, the RCs and The Wellcome Trust are exploring needs
and opportunities in relation to zoonoses and the ecology on infectious
disease. The Research Councils are working with policy partners
on the LWEC Programme (Paragraph 56).
61. Poverty and population migration are
common to many communicable diseases. Consequently, interventions
to reduce poverty, such as increasing access of women to primary
education, might be expected to reduce transmission and disease
incidence. However, experimental interventions have not always
demonstrated the desired effect. This experience points to the
complexity of causes and the need for a deeper understanding of
causative and modifying influences.
62. Social reactions such as stigmatisation
can influence a community's reaction to people with conditions
such as HIV, other STIs and TB. They also affect the response
of people at risk and patients to prevention and health care services.
Research to understand the roots of such belief systems makes
an important contribution to the design of culturally appropriate
interventions.
63. Many commentators agree that disease
prevention requires multidisciplinary, multisector, systems approaches
in addition to specific biomedical technologies. The UK has academic
strengths in the evaluation of health services and public health
interventions, environment and health research, social, health
economics and health policy research applicable to understanding
health systems.
64. It is clear that at an international
level, much remains to be done to achieve effective "joining-up"
for one infection, let alone across diseases and systems. Logically,
the WHO should be best placed to create a roadmap for global control
of malaria, or influenza, that can be subscribed to by the major
players. UK preparations for responding to pandemic influenza
may provide a test bed for coordination at a national level.
8. Cases of Tuberculosis fell progressively
in the UK until the mid-1980s but started to rise again in the
early 1990s. Around 6,500 cases are now reported each year, an
increase of about a quarter since the early 1990s. What are the
main factors of the revival of Tuberculosis infections in Britain?
And how could intergovernmental action help to reverse the trend?
65. The UK HPA reports that TB rates in
the United Kingdom are higher now than at any other time since
1987, and are also higher than those in most other western European
countries. Fortunately, UK rates of both resistant and MDR strains
of TB have remained stable for the past few years and MDR rates
are lower than other countries in Western Europe.[43]
66. 8,497 TB cases were reported in the
UK in 2006, with an incidence of 14.6 per 100,000 of the population
as compared to 11.6 in 2000. The incidence was 44.8 per 100,000
in London, and 72% of all cases occurred in individuals born outside
of the UK. TB outbreaks in schools and local communities highlight
the risk of local spread. Within the indigenous UK population,
many cases are in HIV co-infected people.
67. The organisation of screening for TB
before leaving the country of origin, or immediately upon arrival,
would assist in diagnosing and treating infected immigrants. (Similar
screening for HIV could also prove valuable now that drugs are
available for treatment. However, many donors including the Global
Fund advocate strongly against requiring disclosure of HIV status
when crossing borders).
68. ESRC research highlights the methodological
challenges of working with recent migrants to the UK (who are
often of no fixed abode) and low income groups (who are often
unwilling to participate in surveys). This experience highlights
the value for RC-researchers of working closely with the NHS (to
access health information) and the Home Office (migrant information).
The newly funded UK Household Longitudinal Survey (UKHLS) will
commence in early 2009. Its large sample size and specific attention
to recruiting from minority groups will contribute to understanding
the distribution of migrant populations in the UK.
9. Tuberculosis is potentially curable by
long-term antimicrobial therapies. Yet the numbers of reported
cases worldwide seem to be rising. Are the necessary medicines
not getting through to patients? What are the barriers to effective
long-term therapy? Are we now seeing infections which stem from
other conditions—eg HIV/AIDS? Or are there other reasons
why a treatable disease should be spreading? How might intergovernmental
action help to deal with this situation?
69. TB diagnosis is difficult, complicated,
labour-intensive and expensive for patients and health systems,
especially where co-infection with HIV is common. Moreover, inefficient
diagnosis means that active cases are infectious for long periods
before treatment starts.
70. The duration of TB treatment is long
and labour-intensive, and achieving compliance is real challenge
in resource-limited, high prevalence settings. Shorter treatment
is needed as well as an effective vaccine.
71. Twenty-three high-incidence countries
account for approximately 80% of all new TB cases. In many of
these, TB incidence continues to rise. Not only is the incidence
of TB increasing globally, but so is that of MDR and XDR resistance
TB.
72. Co-infection of TB and HIV is particularly
widespread in southern Africa, with estimates that 50% of new
adult cases of TB are also HIV-positive. In some TB hospital settings,
over 80% are co-infected. Co-infection enhances the progress of
infection to active disease. Commentators point to the importance
of a health systems approach in tackling the complexities of co-infection,
particularly in resource poor and crisis settings.
73. The World Health Organisation has played
a leading role in developing the current strategy of Directly
Observed Treatment—Short course (DOTS) to improve adherence
and response to treatment and to prevent the development of resistance.
WHO led the development of the global Stop TB strategy and is
a leading partner in the Stop TB Partnership, which aims to eliminate
TB. The Global Fund and World Bank are among the other international
partners. There is concern about selection and transmission of
untreatable drug-resistant strains as a result of inefficient
treatment.
74. There is no single mechanism to address
all the issues. Better faster diagnostics are essential to replace
the current sputum microscopy so inefficient in resource poor
settings. So too are novel drugs that act more quickly, and an
effective vaccine. Development of these tools is limited by a
lack of understanding of the fundamental underlying biology of
the processes of infection, susceptibility, immunity and disease
progression.
10. To what extent do you believe that the
2004 Stockholm Convention limiting the use of DDT against Malaria-carrying
mosquitoes has been a factor of increases in the spread of the
disease? Has any risk analysis been carried out comparing the
relative dangers to human health posed by DDT and Malaria?
75. Comparing the risks to people of DDT
as used in malaria control campaigns and of uncontrolled malaria,
DDT is relatively safe—although special measures are need
to mitigate occupational risks. There is no doubt that spraying
with residual insecticides such as DDT had a substantial effect
on malaria transmission although there were concerns about the
development of DDT resistance. The cessation of its use, together
with the absence of alternative control measures, has had a significant
deleterious effect on the spread of the disease.
76. While DDT use against malaria had very
clear human benefits, these were set against the long term environmental
risks, which were substantial and were given priority over the
public benefits.[44]
11. What intergovernmental action is planned
or in hand for early detection of the transmission of Avian Flu
from birds to humans and of human-to-human transmission in potential
source countries? Is this proving sufficiently effective to prevent
an Influenza pandemic? What more could be done?
77. The World Health Assembly 2005 imposed
on member states the obligation to detect and report cases of
H5N1. WHO is helping to coordinate the increased capability of
member states to do this, for example by establishing Regional
H5 Influenza Centres and promoting training etc, financed especially
by the US and World Bank. Progress is gradual; it is unlikely
to prevent a pandemic, but should allow better implementation
of pandemic plans, ameliorating its impact.
78. The WHO has published guidelines, informed
by UK experts amongst others, on diagnosis, treatment, surveillance,
infection control and vaccines.
79. The WHO advises vaccine manufacturer's
on the composition of seasonal influenza vaccine, based on the
advice contributed by, among others, the WHO Influenza Collaborating
Centre established at the MRC National Institute for Medical Research
60 years ago. The Centre monitors changes in influenza virus isolates
that have significance for human health and protection as those
changes occur. Led by Dr Alan Hay, the Centre works closely with
the HPA and with the three other WHO Collaborating Centres (USA,
Japan and Australia) and the global network of National Influenza
Centres. The 50-year old system of virus sharing that has worked
on goodwill was challenged during 2007 by Indonesia, which has
the majority of the world's confirmed human cases of H5N1 and
is seeking guaranteed access to affordable vaccines created from
Indonesian virus isolates. WHO is working with pharmaceutical
companies and governments to put together a package to help developing
countries respond to a pandemic.
12. To what extent do you consider that the
rise in infections in the four diseases is attributable to increased
microbial resistance to antibiotics? What intergovernmental action
is taking place in this area?
80. The history of malaria control offers
many lessons. Emergence of parasite resistance to chloroquine
and sulphadoxine pyrimethamine has contributed significantly to
the failure to control malaria, especially in Africa. Some experts
consider recent deployment of artemisinin combination therapy
(ACT) for malaria—together with mosquito control (eg ITNs)—appears
to be turning the tide. Others are less optimistic, not least
because they are concerned that the availability of ACT is limited.
Moreover, counterfeit ACT is readily available. Combination therapies
for HIV, TB and malaria can be expected to delay the emergence
of drug resistance but not prevent it. Consequently the search
for new classes of drug must continue. There is also a need for
swifter translation of knowledge of drug susceptibility and resistance
into effective policies and implementation on the ground.
81. International organisations have an
important role in identifying and promulgating best prophylaxis
and treatment policies and practice; validating and implementing
standardised resistance testing; and in stimulating, coordinating
and funding the development of new classes of drug. We are not
in a position to comment on the effectiveness of international
coordination.
82. Within the UK, the MRC manages a £16+
million initiative on translational infections research. The initiative
was launched and coordinated by the UK Clinical Research Collaboration.
MRC, the Department of Health and the Wellcome Trust have each
committed £5 million to a joint programme of research, with
BBSRC and the devolved administrations contributing the remainder.
In addition, opportunities for collaboration with Canadian Institutes
for Health on novel antimicrobials are under consideration. The
UKCRC programme builds on—and also address gaps in—the
funders' individual initiatives in healthcare associated infections
and antimicrobial resistance. However the scope of the initiative
is broader than these two topics alone.
13. In a number of countries, including the
UK, there is a problem with hospital-acquired infections. What
intergovernmental sharing of knowledge is taking place to help
bring this problem under control?
83. Please see the answer to the previous
question. In relation to infection control, this question opens
up a set of issues particular to healthcare settings, whereas
the control of HIV, TB, malaria and pandemic flu is based largely
in the community and at a population level. The RCs are not best
placed to address the particular question about IGO sharing of
knowledge.
14. Are there any difficulties with regard
to patents or intellectual property which are impeding the flow
of medicines or other control methods to those infected? Is intergovernmental
action needed to improve the situation?
84. The research community has an interest
in the Trade Related Intellectual Property Rights Agreement, under
which developing countries can gain affordable access to generic
versions of licensed drugs, while protecting innovation and new
product development. The supply of affordable quality drugs is
also important for clinical trials funded by MRC and partner organisations
such as the EDCTP.
85. IP represents a major issue in the provision
and use of genetically engineered H5N1 candidate vaccine viruses
that has had serious repercussions on international co-operation.
It is being strenuously addressed at the intergovernmental level.
(See paragraph 79).
15. What interchange exists between States
in regard to knowledge of and training in the diagnosis and treatment
of the four diseases or regarding preparations for dealing with
outbreaks? What improvements might be made through intergovernmental
action?
86. WHO has a leading role in standardising
practice and training, mostly through short-courses and workshops
(involving RC scientists and laboratories). However, a move to
long-term in-country capacity building is needed. This could start
with improving basic nurse and physician training, then long-term
epidemiology and laboratory career development programmes. Several
UK institutions are involved with distance learning to complement
in-country training and there are undoubtedly opportunities to
do more.
87. The MRC through the Gambia laboratories
and Unit in Uganda contributes to building capacity in clinical
practice as well as research. Recent developments include the
capacity development initiatives of The Wellcome Trust and the
EDCTP.
16. The International Health Regulations 2005
are intended to provide a global framework for the rapid identification
and containment of public health emergencies. How effective do
you consider this response system to be? Do improvements need
to be made?
88. In relation to influenza, these regulations
seem to have omitted an essential requirement: the provision of
assistance to developing countries in developing the capacities
to fulfil their international obligations.
17. What intergovernmental planning has been
undertaken to cope with the impact of an outbreak of infectious
disease caused by deliberate release of micro-organisms into the
environment? Is there adequate liaison between the various agencies
involved, including intelligence, law enforcement and health care
professionals? How could action by intergovernmental bodies help
further?
89. The links between human health and global
security concerns has been recognised as an issue requiring further
research in the context of the new Cross-Council Global Threats
to Security programme.
18. Though our remit is focused specifically
on known infectious diseases, we would be interested to know how
you view the global threat from new or previously unrecognised
ones and from the transmission of infections from animals to humans
90. Many infectious organisms of wild and
domesticated animals are unable to infect humans, or if they do
they rapidly disappear without causing disease. Evolution of strains
of these organisms able to infect man, cause disease and be transmitted
to other humans is inevitable but unpredictable. Mutations are
most likely to occur in viruses than other micro-organsims, because
of their relatively high reproductive rate. But the acquisition
by bacteria of DNA from other bacteria can give rise to strains
with new or augmented virulence and drug resistance.
91. Zoonotic transmission of new pathogens
to man requires susceptible humans to be in association with infected
livestock or wild animals—or vectors such as man-biting
insects. Certain lifestyles (hunting and certain farming practices)
and population movements (civil conflict, famine) can all mediate
the emergence and maintenance of zoonoses. Environmental change
including that consequent on climate change will inevitably change
patterns of human-animal contact.
92. West Nile encephalitis, monkey pox,
Ebola viruses, Chikungunya virus, SARS, HIV and human H5N1 flu
are examples of zoonotic diseases (although human H5N1 has to
date not acquired the property of easy human-to-human transmission).
New zoonoses can be expected. Zoonoses that can evade early detection
and in which disease has an unremarkable onset pose a greater
threat than the dramatic, sudden killers. Most zoonoses lead to
small, localised outbreaks in groups at risk, but the possibility
of more general epidemics cannot be excluded.
93. Bovine TB is strictly regulated by test-and-slaughter
policies in most developed countries, but there is little or no
regulation in most developing countries. The economic and health
benefits associated with reduced productivity of livestock and
transmission to humans are largely unknown.
94. New zoonotics are inevitable. But their
source, scale, timing and visibility are unpredictable. A high
degree of international cooperation is required to identify and
control emerging zoonoses at an early stage. This is an important
responsibility of the WHO, the World Organisation for Animal Health
and the Office International des Epizooties (OIE) in partnership
with national animal and human health surveillance systems. As
noted elsewhere in this response, such systems are barely functional
in many LICs and need to be given higher priority by governments.
95. NERC, MRC, BBSRC and The Wellcome Trust
are currently considering whether there are opportunities to promote
effective new collaboration across their research communities
on the ecology of infectious disease and zoonoses in particular.
19. What resources (subscriptions, staff,
training, medicines etc) does the UK Government commit to intergovernmental
bodies to help in the fight against the four diseases listed?
96. The WHO-designated laboratory at NIMR
and other influenza laboratories in the UK provide substantial
support to WHO in the provision of expertise, training and reagents
to promote international co-operation against flu.
20. Do you wish to provide any other relevant
information in addition to what you have said in answer to the
above?
97. Note that the UK part of the circulation
list below is somewhat restricted to England. It may be helpful
to contact the Royal Society of Edinburgh (which has done a study
on pandemic influenza) and experts on infectious disease within
Glasgow/Edinburgh Universities. It might also be helpful to consult
experts award-holders listed at Annexes 3 to 6.
RCUK
21 January 2008
32 Health is Global: Proposals for a Government-wide
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Foresight. Infectious Diseases: Preparing for the Future. Executive
Summary. Office of Science and Technology. 2005.
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