Memorandum by University College London
1. A recent report on Communicable Diseases
by the UK Department of Health 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?
Post-war optimism was founded on declining death
rates from infectious diseases due to improved social and housing
conditions, vaccines and antimicrobials. Despite these improvements,
infectious diseases remain a major cause of morbidity and mortality
and the decline in disease burden in the developed world has not
been matched in many parts of the developing world. Globally infections
cause over a fifth of all deaths and a quarter of all illnesses
and disproportionately affect resource-poor countries. Worldwide
it is estimated that around 5.5million people die from HIV, TB
and malaria and over a million children die from vaccine preventable
diseases. Should an influenza pandemic occur the vast majority
of deaths would be in resource-poor countries. In the UK infectious
diseases account for over 10% of deaths and a third of consultations
in Primary Care.
In the last few decades, we have witnessed the
unpredictable emergence of major new public health threats such
as HIV, SARS and antimicrobial resistance. Globally, we have failed
to achieve comprehensive vaccination coverage (or achieve eradication
eg polio) or deliver effective therapeutics. This has resulted
in a failure to control transmission and/or effect cure eg TB,
Malaria, Hepatitis B. The continuing emergence of new classes
of antimicrobial resistance in a range of infections (eg MRSA,
TB, Malaria and more recently HIV) and the absence of discovery
of novel classes of antibiotics for common bacterial infections
present further threats. The ever present possibility of a major
flu pandemic, while not new, poses real challenges for control,
clinical management and potential social and economic impact
2. What reliable data exist regarding the
numbers of people infected globally with the four diseases[2]
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?
Surveillance data are collated from State surveillance
systems by WHO. For HIV, data are also collated by UNAIDS. Significant
investment goes into providing estimates of the burden of disease
based on a variety of sources (eg diagnosed cases, sentinel laboratory
data, ad hoc surveys). For example for HIV this includes incident
cases of AIDS and AIDS deaths, new diagnoses of HIV and community
surveys of the prevalence of infection.
The incidence of flu is highly seasonal and
much infection never comes to the attention of health care professionals.
Knowledge of the particular type of virus circulating is based
on a network of participating laboratories coordinated by WHO.
Ultimately, even the best surveillance systems will not record
all cases and the quality and completeness of surveillance data
varies considerably around the world. For example, case definitions
may vary according to available resources, eg smear vs culture-confirmed
TB. Surveillance data are also limited in terms of the risk factor
and outcome data collected. International figures are therefore
"best estimates" of the burden of disease and take into
account assessments of the completeness of data etc. Of the surveillance
systems for the four diseases, that for HIV/AIDS is probably the
most comprehensive.
We do not present here detailed trends for the
four infections as these are best reported and are widely available
from those specifically responsible for national and international
surveillance.
In the case of HIV, we note the continuing transmission
in all parts of the world. Transmission of all infectious agents
depends on the interaction between the biological properties of
the organism, particularly its ease of transmission, the characteristics
of the population into which it is introduced (size, density,
living conditions, sanitation etc) and human behaviours, individually
and collectively.
The HIV epidemic, for example, is driven primarily
by patterns of sexual behaviour, particularly unprotected sex
and rates of partner change as well as the high incidence of untreated
sexually transmitted infections in the worst affected parts of
the world. Underlying trends in sexual behaviour are many social
and economic factors including poverty, migration, conflict, social
position of women and education. These problems are compounded
by the lack of health systems infrastructure to deliver prevention
and treatment programmes.
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?
Warning of outbreaks of infectious diseases
are largely coordinated by WHO through their international surveillance
systems which draw data from State surveillance systems. Recent
UK reports recognise the importance of investment into coordinated
international surveillance systems. The Office of Science and
Innovation Foresight Report "Infectious Diseases: Preparing
for the future" emphasised the importance of harnessing new
technologies for detection, identification and monitoring (DIM)
systems for early detection of the appearance of disease, rapid
and accurate identification of infectious agents causing outbreaks
and monitoring of control programmes. Foresight also recognise
the importance of interdisciplinarity in the surveillance and
control of infectious diseases "Understanding the future
risks of infectious diseases, and how best to use DIM to help
manage those risks is an interdisciplinary problem. A key challenge
is to bring together relevant skills expertise to deliver properly
integrated scientific research and development and to provide
suitable opportunities for capacity building"; "How
DIM technology is used is just as important as the technology
itself and considerable benefits are foreseen from improving the
systems in which the technology operates".
Both WHO and Foresight identify a need for greater
investment in surveillance capacity in poorer countries. Similarly
the recent Nuffield Council on Bioethics Report on Public Health:
Ethical Issues recommended that "countries such as the
UK should seek to enhance the capacities of developing countries
to conduct effective surveillance of infectious diseases",
a recommendation guided by the ethical framework of the stewardship
model.
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?
Infectious disease will continue to be driven
by existing burden of disease in different populations, as well
as the level of immunity to specific infections through vaccination
or natural infection. Despite massive investment in prevention
and treatment programmes in many parts of the world HIV transmission
continues at high levels. Even in the UK where prevention and
treatment programmes are well developed compared with parts of
the world most severely affected such as Africa, transmission
of infection is continuing, particularly amongst homosexual men.
While great progress has been made in the distribution
of antiretroviral therapy to reduce morbidity and mortality from
HIV, there remains an urgent need for greater integration of prevention
and treatment efforts to reduce transmission and recent spread
to parts of the world that previously had limited epidemics. The
emergence of antiretroviral resistance is a further concern. This
will need both careful surveillance and monitoring of roll-out
of antiretrovirals for maintenance of appropriate drug supplies
and effective clinical management programmes.
Reliable predictions about the timing or extent
of an influenza pandemic cannot be made and their remains great
uncertainty about our ability to contain the spread of the emergence
of a transmissible and virulent new strain, although significant
progress has been made in the development of pandemic plans. These
plans tend to be more poorly developed in resource poor settings.
Many predictions are based on mathematical models. These are important
in exploring future scenarios but are based on a range of assumptions,
themselves using incomplete surveillance and/or behavioural data
and often have wide uncertainty limits.
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?
Control is likely to be influenced by wider
global issues, eg economic conditions, political imperatives,
religion, climate change, war and conflict. Blockages to progress
need to be considered in the context of the broader agenda of
health inequalities. Social and economic determinants of transmission
are key factors in the transmission of all four diseases. That
said, blockages to progress include the lack of health infrastructure
in many parts of the world to institute population programmes
for control, the need for integrated prevention and treatment
services. In the case of HIV there is a need for continued and
population-wide prevention programmes accompanied by high level
commitment from governments, and the availability of effective
distribution systems for the delivery of both prevention and treatment
interventions. Generally, intergovernmental support to make affordable
drug and vaccine supplies available are critical.
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?
University College London is a multi-faculty
university. Our primary role is in research and education. We
undertake multidisciplinary research, exploring pathogen, host
and societal impacts on the spread of infections both through
our large Faculty of Biomedicine, as well as through anthropology,
economics, geography, the built environment etc. Our work has
a particular focus on HIV and TB and more recently on influenza.
Our clinical scientists, in addition to their clinical care of
infectious diseases (with a strong focus on HIV), undertake observational
and experimental studies of the impact of therapy on the clinical
outcomes. Our laboratory scientists are engaged in a wide range
of research including vaccine development and the national and
international surveillance of antiretroviral resistance. We have
an international programme of studies into the behavioural determinants
of HIV acquisition through studies of sexual behaviour in high
risk and general population groups and behavioural intervention
studies in both a UK and international setting. We are involved
in international trials of tuberculosis treatment. With the Medical
Research Council clinical trials unit we participate in trials
of HIV antiretroviral delivery in UK and Africa and of evaluation
of the efficacy of vaginal microbicides in preventing HIV transmission.
We are undertaking studies in the UK to better understand the
transmission of seasonal influenza and developing collaborations
with international colleagues.
In recent years we have enhanced our interdisciplinary
collaborations. Through our newly formed Institute for Global
Health, we are promoting cross-faculty links within UCL and wider
international collaborations to extend our educational and research
programmes in effective interventions for the control of infectious
diseases.
Many staff at UCL contribute to national and
international policy through engagement with Government advisory
bodies (eg National Expert Panel on New and Emerging Infections
(NEPNEI), Specialist Advisory Committee on Antimicrobial Resistance,
Expert Advisory Group on AIDS, Foresight), advice to funding bodies
(eg MRC, Wellcome Trust, DFID) and to international groupings
(eg WHO, CDC). We collaborate closely with colleagues at the Health
Protection Agency and undertake joint programmes of research.
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?
As indicated in our previous responses, social
and economic factors are major influences on the spread of infectious
diseases. Sexual behaviour patterns are critical to HIV spread,
but these in turn are driven by demography, migration, status
of women etc. War and Civil conflict have a major impact on disease
control programmes. Migration facilitates the transmission of
all four diseases but is particularly important in the rapid dissemination
of emerging outbreaks such as pandemic flu where early detection
is critical to control.
The interaction between the HIV, TB and malaria
epidemics exacerbate one another and greater joining up of programmes
is needed which take greater cognisance of social, economic and
behavioural drivers. Alleviation of poverty is important in all
these conditions but there is a particular need to focus on raising
education levels and training clinical and public health personnel
to implement effective evidence-based programmes.
In some settings drug use and addiction related
problems exacerbate the problem eg as a direct risk factor for
disease or complicating management.
Global warming is likely to impact directly
on the transmission of some infections, eg the geographical extension
of malarial zones. It is also likely to create the social and
economic conditions which will result in food insecurity, population
migration and national disasters which enhance the spread of infectious
agents and hamper control programmes. All these are major challenges
which require the engagement of many disciplines (eg economics,
political science, geography and the built environment), government
departments, and intergovernmental working in identifying sustainable
solutions.
Greater interaction between experts in animal
and human health is needed in tackling some of the newly emerging
infections, eg SARS, avian influenza to ensure that early warning
systems are in place, to limit the risks of outbreaks and to improve
control measures.
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?
The majority of tuberculosis cases in the UK
occur in those born abroad. Migrants to the UK tend to come from
areas with high tuberculosis incidence: of the top 10 source countries
of recent immigrants to the UK, six have a tuberculosis incidence
of over 150/100,000 population. In addition, there is considerable
travel from the UK to visit friends and family abroad, particularly
to the Indian Sub Continent.
It is tempting to think that the solution to
the problem lies in screening of new entrant groups but there
are difficulties with this approach. The majority of foreign-born
patients who develop tuberculosis do not have active disease on
arrival and may only develop this years later. Identification
of TB risk may perhaps be better tackled by a process that begins
with the new entrant check when individual register with primary
care and by ensuring ready access to high quality tuberculosis
services when needed.
Work published in the New England Journal of
Medicine demonstrates the "Enlightened Self Interest"
phenomenon whereby rich countries can achieve greater reductions
in their domestic levels of tuberculosis at a lower cost by investing
in control overseas than by screening new migrants. Schwartzman
K, et al, N Engl J Med. 2005 Sep 8;353(10):1057-9. Intergovernmental
action to strengthen tuberculosis control in resource poor countries
is fundamental to global control.
A relatively small but very important group
of patients with overlapping risk factors of illegal drug use,
homelessness and imprisonment make a significant contribution
to transmission particularly in major urban settings. Such patients
tend to be diagnosed late, have highly infectious disease and
poor compliance with treatment leading to transmission and the
development of drug resistant disease. More action is needed to
ensure that tuberculosis services can engage effectively with
this group.
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?
Maintaining drug supplies for TB is an essential
pre-requisite for control but clinical delivery is difficult because
effective treatment requires at least six months of uninterrupted
treatment and adherence is often poor. Directly Observed Therapy
(DOTS) has been widely adopted as a strategy globally to ensure
patients take their treatment but there remain challenges in delivering
effective DOTS programmes in different settings
Tuberculosis incidence has risen sharply in
countries with severe HIV epidemics. HIV increases the risk of
TB, through immunosuppression, but also indirectly, through onward
transmission of M tuberculosis from the increased caseload.
Wide scale rollout of antiretroviral therapy (ART) is needed.
However this alone is unlikely to reverse the rising incidence
of TB, since the increased risk of TB occurs soon after HIV seroconversion,
before ART is likely to be given. Enhanced active case finding,
for both HIV positive and HIV negative individuals, needs to complement
a sustained TB control programme based on the DOTS strategy. HIV
and tuberculosis programmes need to work together, including screening
for symptoms of tuberculosis as part of HIV counselling and testing.
The impact of innovative approaches, such as mass isoniazid chemoprophylaxis
and novel diagnostic methods, need to be investigated. Only with
a shift in paradigm, while continuing measures that have been
shown to be effective, are we likely to reduce the risk of tuberculosis
in HIV-infected individuals, and reduce transmission in the population
as a whole.
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?
No response.
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?
Although there is relatively intensive activity
to identify spread from birds to human and subsequent human to
human spread it is possible that identifying and acting around
such incidents may delay rather than prevent a pandemic. If a
strain that is well adapted to humans emerges and spreads efficiently
from person to person then intergovernmental co-operation may
ameliorate impact but is unlikely to stop it.
Stockpiling of antivirals is a key part of many
countries' pandemic response but emergence of antiviral resistance
threatens to limit their impact. Better international surveillance
of antiviral resistance in influenza is needed. Even in the absence
of antiviral resistance their use may have limited impact on disease
transmission. Antivirals have however been found to be effective
at preventing contacts of influenza from developing active disease
but their use in this capacity does not seem to be being considered.
Better understanding of how non-pharmaceutical interventions can
interrupt transmission (eg hand hygiene, surface cleaning, mask
use etc) needed. This could be addressed through large scale community
studies of interventions to prevent influenza transmission using
seasonal influenza as a model..
International co-ordination of the key data-sets
and specimens that should be collected around early cases of avian
influenza in humans is needed. There are also political and "scientific"
sensitivities about sharing of such data which need to be overcome
if we are to understand the problem better.
For example, the Nuffield Working Party on Public
Health Ethics drew attention to the issue of sharing virus isolates
internationally in the control of pandemic flu. "WHO should
not merely facilitate access to virus isolates for commercial
companies, leaving the question and availability of vaccines to
market forces. It should use its authority to impress on pharmaceutical
companies their social responsibilities. We urge WHO to explore,
in liaison with Governments and relevant industries the notion
of viewing virus isolates as a form of "public good"
and to take a flexible approach to patenting and intellectual
property protection".
Investment in planning for research that would
be conducted in the event of a full-blown pandemic is needed.
Without such planning it will be difficult to conduct clinical
research in a pandemic situation, especially within modern research
governance structures.
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?
In these four diseases antimicrobial resistance
is an important problem but is unlikely to be a key driver of
increases in cases. It can however, make cases substantially harder
to treat. Although outside the scope of the four diseases, antimicrobial
resistance in common bacteria such as Staphylococcus aureus
infection and Escherichia coli is a major emerging
threat. Antimicrobial resistance has been a problem in hospitals
for many years and there is increasing evidence that resistant
strains are now becoming important community pathogens. Surveillance
systems are often not well equipped to identify this because they
tend to focus on isolates from secondary care settings. The problem
of antimicrobial resistance in resource countries poor countries
where prescription of antibiotics is unregulated has not been
adequately studied.
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?
Although there have been initiatives to encourage
sharing of ideas in infection control between countries and there
are a number of EU funded projects in this area it seems that
more could be done to understand international variations in hospital
acquired infections and to develop research networks that are
able to investigate these in a more systematic way.
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?
See response at 9 and 11. We also note the important
rolls of community organisations, NGOs etc in campaigning for
the equitable delivery of affordable medicines for eg the African
Treatment Action Campaign for access to antiretroviral therapies.
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?
Recent reports have highlighted the need for
international cooperation in training and capacity development
in resource-poor settings (For example Crisp Report and Chief
Medical Officer's report on global health). There is undoubtedly
a need for capacity and infrastructure development in this area
in developing countries. Research funding agencies are beginning
to address this through new capacity development funding inititiative
encouraging North-South and South-South research partnerships
(eg Wellcome Trust, MRC).
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?
No response.
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?
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.
Whilst there has been much pandemic planning
in relationship to flu it should be recognised that other pathogens
possibly new to human-pathogens could lead to a pandemic. There
is therefore a need to consider "generic" pandemic plans
that would be of use whatever the infection.
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?
20. Do you wish to provide any other relevant
information in addition to what you have said in answer to the
above?
No.
February 2008
2 HIV/AIDS, Tuberculosis, Malaria and Avian Influenza. Back
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