Memorandum by the London School of Hygiene
& Tropical Medicine (LSHTM)
Comments concerning malaria are addressed
in the memorandum from the Malaria Centre, LSHTM
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?
1. The assessment of the DoH is relevant
and the world remains a long way from conquering infectious diseases
although significant progress has been made in a number of areas.
Through antibiotics, antimalarials and vaccines, the spread of
CD has been curbed, notably in the developed world. However the
optimism that heralded the use of effective medical interventions
has dwindled with the emergence of widespread and increasing resistance
to many treatments and the emergence of new diseases such as HIV/AIDS.
The burden of infectious diseases remains high, especially in
developing countries and particularly high for children. Increasing
travel, the proximity of individuals to each other, urbanisation,
changes in land use and economic pressures including in the production
of food all impact on the emergence of new diseases and the re-emergence
of ancient diseases like TB. These factors and others are changing
the global pattern of infectious diseases, notably zoonoses and
infectious diseases spread between humans—micro-organisms
can spread more rapidly and become global in a matter of weeks.
Threats now are greater than ever. The impact of global poverty,
climate change, population growth, population movements, the globalisation
of trade and changes in land use to name a few are impacting on
the emergence and spread of many diseases. Globalization and forces
of global change have intensified cross border activity to such
an extent that it undermines the capacity to control them. In
many ways national borders have become irrelevant. And whilst
responses to infectious diseases are principally grounded in notions
of sovereignty, the international nature of many infectious diseases
challenges state-framed responses.
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?
2. Data exist although much of the data
are estimates because surveillance systems are inadequate or very
limited in capacity, notably in the developing world. Information
gathering remains a challenge, for technical but also political
reasons. This was illustrated recently by the change in total
estimate of people living with HIV/AIDS (PLWHA) by UNAIDS which
reduced its total estimate from 40 million people to 33 million
people. In addition to global surveillance frailties, technological
challenges mean that estimates may be somewhat uncertain. For
example, the estimate of 8 million annual cases of active tuberculosis
is largely drawn from technologies used for more than 100 years
of microscopy (rather than more sophisticated and more accurate
novel technologies); the estimate of one third of the world's
population being infected with the organism that causes TB is,
likewise, based on old techniques that lack sensitivity and specificity.
Changes in trends depend on a large number of
factors, from upstream causes such as poverty and the complex
drivers of poverty (for example for TB and HIV) or poultry trade
(for avian influenza) to more downstream causes such as misuse
of antimicrobials and failing health services in the increasing
generation of drug resistant organisms, for example multidrug
resistant TB. A more positive example, is the effectiveness of
antiretroviral treatment for people infected with HIV. However,
the emergence of drug resistant HIV is a particularly worrying
scenario. By reducing mortality, prevalence of HIV has increased.
This has happened even where incidence has remained stable.
Tuberculosis rates are declining (too slowly)
all over the world although some find this hard to believe for
the African continent, where rates have risen hugely with HIV
over the past decade. The centre of the HIV pandemic has drifted
south into Southern Africa. It remains a huge challenge in most
sub-saharan African countries. Elsewhere, HIV is a major public
health threat but is largely confined to particular sections of
the population and in only a few places have generalised epidemics
developed.
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?
3. WHO is running the GOARN (Global outbreak
alert and response network) which is relying on government declaration
but also on media report and uses the web to identify early signs
of outbreaks. With the introduction of the International Health
Regulations, countries are now obliged to report on serious public
health threats with potential to spread beyond a country's borders.
WHO is also working at the strengthening of national surveillance
capacity, for specific diseases, sometimes using other disease
surveillance system as the backbone for country surveillance.
However countries with poor surveillance systems pose a threat
to the effectiveness of global surveillance. Europe also has an
early warning and response system. The experience of SARS and
improvements in surveillance such that informal reports of potential
problems are highlighted suggests global surveillance has improved
markedly in the past decade. But weak surveillance capacity and
a lack of integration between animal and human health surveillance
systems remains a challenge.
For HIV and tuberculosis outbreak management
plays little current role in disease control. Although there is
little doubt that there are many outbreaks of TB ongoing particularly
in health care settings, the background rates of transmission
in the community have meant that these are not the priority in
high burden countries. The arrival of multi- and extensively resistant
tuberculosis have alerted disease controllers to the need for
interventions to reduce the risk of transmission in congregate
settings. This is an area where much more work is needed, even
drug sensitive TB is probably transmitted commonly, particularly
in places where HIV and TB are co-epidemic.
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?
4. In the area of infectious diseases, it
is challenging to make predictions and many scientists have been
proved wrong in the past doing just this. The early predictions
based on transmission dynamics modelling of the unfolding HIV
epidemic bear witness to this, predictions which were much more
grave than reality has shown in the developed world and other
areas beyond sub-Saharan Africa. The challenge stems from our
lack of understanding of the complex interplay between man, organism
and environment including socio-economic development, human behaviours
and medical interventions. Some interventions can be very effective,
such as vaccinations and for instance an HIV or a malaria vaccine
would change dramatically the patterns of the diseases. Other
interventions are more problematic to evaluate such as prevention
interventions. The persistence of underlying factors for the spread
of the main diseases and the acceleration of some of these such
as intensification of global human movements means that spread
could potentially accelerate in the coming years. For HIV, a vaccine
remains at least a decade off. Treatment, where available, is
keeping many people alive and productive. But many people remain
unaware of their HIV status, and this has consequences both for
their individual health and public health. The reasons why people
do not seek testing are unclear. For pandemic influenza, a pandemic
will occur but when remains uncertain. Other unforeseen infectious
diseases will also emerge just as SARS and HIV did.
HIV—incidence has probably peaked some
years ago, but the long period between infection and disease means
that HIV-related illness will be a major part of the health care
burden for many years to come. The more successful we are at scaling
up anti-retroviral therapy, the greater that burden will be—there
are still thought to be at least 4 new infections with HIV for
each person starting on ARVs, so systems will become increasingly
stretched to scale-up and deliver chronic care.
Effective TB control with sufficient investment
should be able to reduce the burden everywhere except Africa.
There may be some areas, where MDR TB leads to more severe problems,
but these remain the minority of cases. In Africa it will take
much longer and more innovative control approaches to make a real
impact on the burden of disease. If MDR becomes common it will
be even more challenging.
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?
5. Blockages are many. They involve money,
politics, morality, science/tools, inter-government relations,
education, economic development. Some are upstream issues such
as economic development and poverty alleviation—seemingly
almost intractable problems. Others are downstream and include
investment in effective drugs for infectious diseases that principally
affect marginalised poor populations.
Briefly, a few examples include:
HIV—adherence, lifestyle issues, cost,
stigma, drug resistance, health services delivery (especially
in Africa).
Flu—animal husbandry, global trade imperatives,
speed and ease of spread; access and cost to vaccines and drugs,
surveillance is stronger globally but response capacity weak esp.
in developing nations.
TB—stigma, HIV, poverty, adherence, resistance,
nosocomial transmission, migration, criminal justice system links,
frail health systems.
The role of inter-governmental organizations
is critical in advancing and advocating evidence-based policies,
in channelling funds to effective interventions, in coordinating
responses to diseases, in supporting the strengthening of health
systems as well as promoting economic and social development and
in evaluating interventions.
Specific information concerning HIV and Herpes
simplex virus type 2 (HSV-2) is included at the end of the document.
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?
6. Principally research (both fundamental
and applied), training, consultancies and citizenship. LSHTM has
a global network of collaborators and extensive experience in
all four diseases ranging from bio-medical laboratory-based research
to policy analysis and intervention support.
Our resources are largely dependent on funding
for research and students. We receive very little for work with
WHO and Global Fund and this limits our ability to support them.
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?
7. The main non -health causes for the spread
of the four main diseases are related and include poverty, fuelled
by population growth and urbanization, environmental changes impacting
land use and access to water, international travel and migration,
global trade, human behaviour and lifestyles (sexual behaviours,
drug use ...). Many international organizations address these
factors which are cross cutting across many areas of interventions.
Specific wide ranging international organizations
are addressing a number of these issues and these include the
World Bank and UNDP as well as bilateral agencies (DFID, AUSAID,
USAID). Other organization are more focused at a more specific
range of issues such as health related issues for the WHO. The
difficulty is that more and more organizations involved in health
try to develop multi-sectoral approaches to both health and development,
which lead to a multiplications of cross sectoral interventions
by actors often in an ill-coordinated fashion. Whilst many organisations
posit the need for coordination what this means in reality is
sometimes unclear. Coordination for what, of whom, for what purpose?
Because donors and agencies wish to see value for money the issue
of attribution is raised. Yet attributing benefit to specific
interventions is problematic, particularly when several interventions
are being implemented (funded by different agencies). The need
for attribution also results in a multiplicity of monitoring and
evaluation systems, the development of vertical implementation
initiatives, and parallel administrative structures to services
agencies. To define clear targets, the UN-MDG (Millennium Development
Goals) were established, many of them cross sectoral. A number
of initiatives have been taken to try to resolve this, notably
with the Paris declaration signed in 2005, that promotes harmonization
of approaches or the setting up of global agencies to channel
funds for specific diseases such as the Global Fund to fight against
AIDS, Tuberculosis and malaria (GFATM), or the increase of the
amount of funds channelled through recipient countries budget
support. However on the ground coordination and harmonisation
of action remain extremely difficult to implement, notably because
poor coordination between donors.
The UK government has highlighted the threats
that climate change poses to health, including through infectious
disease [Stern Review, etc] The Fourth Assessment Report of the
Intergovernmental Panel on Climate Change (2007) reviewed the
evidence for early effects of climate change on biological systems,
including arthropod species, in terms of changes in distribution
and seasonal activity. School staff have played an important role
in the IPCC. Although evidence on movement of disease vectors
is currently limited (due to lack of long term surveillance data)
the IPCC concluded that the northern limit of many tick species
may have moved due to climate warming in Europe and Canada. Although
it is not possible to attribute single outbreaks to long term
changes like climate change (eg chikungunya), there is good evidence
the shifts in the current distribution of the animal disease bluetongue
in europe has been facilitated by climate warming. [ref Purse
B V, Mellor P S, Rogers D J, Samuel A R, Mertens P P, Baylis M.
Climate change and the recent emergence of bluetongue in Europe.Nat
Rev Microbiol 2005 Feb; 3(2):171-81. Erratum in: Nat Rev Microbiol
2006 Feb; 4(2):160].
Several reports by WHO and other agencies have
stressed the importance of strengthening systems for infectious
disease surveillance and responses a key intervention for health
protection from climate change. WHO has consistently argued that
such strengthening should, as far as is possible, build on existing
surveillance systems and regulations (such as the new International
Health Regulations), rather than replicating existing functions.
WHO has highlighted the need for systematic reviews of the suitability
of existing surveillance and response systems, at national, regional
and global levels, to meet the additional challenges of climate
change.
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?
8. A total of 8,497 tuberculosis cases were
reported in 2006 in the UK, a rate of 14.0 per 100,000 population.
Both the number of cases and the rate in 2006 were very similar
to those for 2005. The London region accounted for the largest
proportion of cases (40%) and had the highest rate (44.8 per 100,000).
The majority of cases occurred in young adults aged 15-44 years
(61%). TB is more prevalent in migrant populations, with 72% of
cases non-UK born in 2006.
In 2006, 7.7% of tuberculosis cases were resistant
to at least one first line drug, 6.9% were isoniazid resistant
and 1.1% of cases were multi-drug resistant. The greatest number
and proportion of drug resistant cases were among those reported
in London. Non-UK born cases had greater overall levels of resistance
than UK born cases, although this varied by region of reporting
and age of cases. In London, isoniazid resistance was highest
among UK born cases (13.7%) (HPA).
Main factors of the revival of TB in the UK
are increased migration from high prevalence areas (South Asia,
Africa) and increased travelling between regions and the increase
in cases of HIV/AIDS, also found in people born outside the UK.
UK TB reflects global epidemiology. Initiatives
such as screening at ports of departure are unlikely to impact
to any significant degree on TB control in the UK. Control in
countries from which migrants originate is needed—TB control
demands a global response. This noted, drug resistance represents
a health system failure. The UK should not be producing drug resistant
disease.
The challenge is twofold—one: provide
more accessible health services for immigrant communities—many
are scared to register with GP, can't explain their symptoms in
English etc etc. Two: improve tuberculosis control worldwide by
joining enthusiastically and with real resources the Global Stop
TB efforts—Gordon Brown launched it, but the funding gap
is still huge. A recent paper in the New England Journal of Medicine
(Menzies et al) showed that for the US, it saved money
to invest in tuberculosis control in Mexico. The same principle
applies in the UK, although our more efficient health care system
may mean that it is not actually cost-saving only cost-efficient.
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?
9. Non-adherence to tuberculosis (TB) treatment
is an important barrier for TB control programs because incomplete
treatment may result in prolonged infectiousness, drug resistance,
relapse, and death. Other barriers include social stigma, costs
of treatment, lack of access to health services, poverty and lack
of social support, notably in developing countries. Prevalence
of HIV is also driving TB incidence up, with TB being the first
cause of death among people living with HIV/AIDS. Other barriers
include lack of diagnosis and poor detection. Another factor for
spreading of TB is institutional spreading (prisons, health care
sector).
Intergovernmental organizations play a major
role in providing diagnosis and treatment protocols to health
care professionals. With the issuance of the DOTS strategy in
1993, WHO has for instance supported the standardization of approach
with a view to provide evidence based diagnosis, treatment, reporting
and drug management protocols and to promote a reduction in non-compliance
and development of drug resistance. Institutions like the GFATM
provide hundreds of million of $ to fund TB programmes in many
developing countries. International organizations have also addressed
the co-infection HIV/TB and encouraged national programmes that
target both diseases. Finally IO have also supported reduction
in drug pricing for TB (and HIV) and enabled poorer countries
to better access expensive drugs such as second line TB treatment.
Challenges include the integration of vertical TB control programmes
into health care systems, and the sustainability of externally
funded programmes if funding ceases. In addition, without HIV
control TB control is likely to remain a mirage. Moreover, a partially
functioning TB control programme, from a public health perspective,
is worse than no programme—the development of resistance
is almost guaranteed—witness former Soviet Union.
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?
11. Under the auspices of UNSIC, the UN
system, the OiE, the World Bank, regional institutions (including
ECDC and AU-IBAR) and national technical institutions work on
the implementation of UN strategy on avian influenza. A consolidated
Action Plan for Avian and Human Influenza (AHI) was drawn up.
Emphasis was put on strengthening surveillance and improving laboratory
capacities, health infrastructures, humanitarian response capacity,
public understanding and bio-safety will impact positively on
the level of preparedness for, and response to, any kind of zoonotic
diseases. UN systems agencies are pursuing seven objectives as
they contribute to effective national, regional and global responses
to HPAI and the influenza pandemic threat (UNSIC).
However the main issue is, for many high risk
countries, the lack of surveillance capacity, the integration
of veterinary and human surveillance, and human pandemic response
strategy development and operational capacity. These weaknesses
are particularly prominent in parts of South East Asia and Africa
where the emphasis has been on avian influenza control rather
than pandemic human influenza control.
There are also issues around the possible duplication
of actions by a myriad of actors who work on this topic.
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?
12. Microbial resistance is increasing for
the three main diseases. Levels of resistance vary according to
the disease and with the geographical location. Drug resistance
rates are higher for TB in Eastern Europe, and for HIV in the
developed world, where a higher proportion of patients are on
second or more line of treatment (though this may be partly artefactual
since resistance testing of HIV is only widely available in the
West). Resistance to first line of treatment for malaria is widespread
and the recommendation by WHO is now to use Artemisin in most
places. Drug resistance represents health system failures—it
is a man-made phenomenon. In the former Soviet Union TB drug resistance
has arisen because of very poorly functioning fractured systems
of care, erratic availability of drugs, bad prescribing by doctors,
and patient's struggling to adhere to treatment. Spread has occurred
because of transmission in overcrowded prisons and pre-detention
trial centres and health care settings. The HIV epidemic in the
FSU will promote further spread with likely disastrous implications
for control of both diseases. Drug resistant HIV is a huge potential
problem, particularly in developing countries where access to
resistance testing, second line drugs, and support systems for
adherence is poor. The development of resistance threatens future
effective responses.
The most critical issue is the necessary monitoring
of drug resistance that is not always implemented, notably in
developing countries where laboratory facilities are lacking and
resources are limited. This is particularly an issue with the
current scale up of ARV treatment for HIV, and millions of patients
now accessing ARV without a clear understanding of the magnitude
of emergent drug resistance. There is a clear need for WHO to
take the lead and to monitor drug resistance, notably for ARV.
The issue is that many countries will not have the resources to
provide second line treatment of their citizens, which means that
many questions go unanswered and that IO do lack longer term perspective
on that matter.
This is certainly a challenge for all these
diseases and requires ongoing investment in basic biomedical science
to continually seek alternative approaches to treatment.
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?
15. States exchange experience and knowledge
often under the auspices of intergovernmental organizations such
as WHO, or within regional structures (EU, PAHO, CIS ...). Sometimes
regional structures collaborate with WHO in joint workshop (EU/WHO
workshop on influenza pandemic for European countries). Regional
collaboration bodies associated with intergovernmental organizations
are a good framework for states to strengthen their knowledge
and expertise for controlling infectious diseases.
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?
16. The new IHR have just come into effect.
They represent a significant improvement over the previous version
of 1969 because they focus on any heath threat of major significance
rather than on a set number of diseases. They also rely not only
on countries declaration of outbreak but on external sources for
information (media report, NGO|) which is more effective.
The limitations are more in the implementation
of the IHR because many countries are poorly resourced and do
not have the capacity to operate an effective surveillance system.
Whilst the IHR have considerably strengthened global surveillance,
it could be argued that response has been less well addressed.
The case of Indonesia and its reluctance to share H5N1 virus with
the international community is a case in point. The IHR have not
offered a way through this. Some countries may be reluctant to
fully collaborate internationally if they perceive that they are
unlikely to benefit equitably in resources (for example vaccines)
that originate from their soil.
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.
18. In the last 25 years WHO identified
at least 25 new diseases. Some always existed but they have been
newly recognized as such (HPV and its role in cervical cancer),
others are truly new diseases such as AIDS and SARS. Microbial
resistance also drives the emergence of novel strains of old diseases,
for example XDR-TB. Environmental changes associated with increase
in travel will also change the geographical distribution of diseases,
leading to developing countries to face diseases that they have
not historically faced (Chikungunya, West Nile virus). Novel diseases
are likely to continue to emerge as they always have, exploiting
changing relationships between man, animals, his environment and
microbe. The transmission of these emerging infectious diseases
is more likely now to become global in nature more rapidly than
ever before in human history.
22 January 2008
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