Memorandum by the Medical Research Council
1.1 In spite of the post-war revolution
in antimicrobials and vaccines, infectious diseases have remained
at the forefront of global morbidity and mortality. The old infections
of malaria and TB have not been controlled; the new disease of
HIV has had a terrifying impact; viruses such as influenza continue
to adapt and re-emerge in forms that exploit changes in human
society. International travel facilitates global spread of pathogens,
and microbes have evolved resistance at a rate that often outstrips
the development activities of the pharmaceutical industry. 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been replaced by appreciation of a two-way process in which disease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.
1.2 (Malaria) There is still no effective
vaccine, and only recently has there been renewed research interest
in the development of new drugs. Following the failure of eradication
campaigns based largely on anti-mosquito measures in the 1960s,
interest in the disease waned. It is only recently that approaches
such as insecticide-treated bed nets and combination drug therapy
are being deployed.
1.3 (AIDS) Over the past 10 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.
2.1 (TB) The WHO and the Global Partnership
to Stop TB maintain realistic data on the number of cases of active
disease. The number of individuals who have been infected far
exceeds those that develop disease; estimates of the number of
infections are very approximate. The incidence of TB increases
dramatically in individuals who are coinfected with HIV. This
has had a major impact on TB in sub-Saharan Africa.
2.2 (Malaria) There have been reasonable
estimates of the number of clinical cases of malaria in Africa
each year but the number of individuals who are infected but without
clinical signs is much higher.
2.3 (AIDS) Yearly estimates of the number
of people infected with HIV-1 and deaths from AIDS are published
every year by UNAIDS/WHO. The 2007 figures show an apparent decrease
in the numbers. However this reflects changes in the methodology
of estimation rather than any real decrease. Determining real
time trends in HIV-1 incidence remains enormously difficult; thus
gauging the success of intervention measures for preventing HIV
spread remains a formidable task.
2.4 (Flu) The WHO Global Influenza programme
coordinates the validation of human cases of H5N1 and provides
up-to-date reports of recent cases. 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.
3. (Flu) WHO coordinates the Global Influenza
Surveillance Network (as well as other infectious disease networks)
that comprises 121 national influenza centres in 93 countries.
Current enhancement of the network includes establishment of regional
reference laboratories in areas previously poorly represented
and additional WHO Collaborating Centres.
4.1 (TB) The Global Plan to Stop TB aims
for a 50% reduction in TB worldwide, in line with the Millennium
Development Goals. This will not be achieved in Africa (due to
HIV-TB) or in Eastern Europe (due to drug-resistant TB). It is
anticipated that economic development in Asia will reduce TB over
the next decade.
4.2 (Malaria) The Gates Foundation has recently
announced a commitment to the eradication of malaria in the longer
term. Whilst current methodology can achieve substantial reduction
in malaria provided that it is delivered to areas of need, there
is also an urgent need for new antimalarials and/or the development
of an effective vaccine to ensure that such success can be maintained.
4.3 (AIDS) In 2006 the UN member states
agreed to work towards the goal of "universal access to comprehensive
prevention programmes, treatment care and support" of HIV/AIDS
by 2010. Provided the promises made are kept, and the goals in
scaling up health sector interventions are met, there is every
prospect of a significant improvement in global HIV/AIDS mortality
figures.
4.4 (Flu) H5N1 is endemic in birds in a
number of countries and it seems likely that sporadic human infections
will continue to emerge. However there is a finite probability
that a pandemic will develop.
5.1 (TB) Diagnosis of TB relies mainly on
a test introduced in the 1880s; the only vaccine for TB (BCG)
was introduced in the 1920s and is ineffective against the major
form of the disease; no new drugs have been developed for TB since
the 1960s. There is a critical need for basic research directed
toward the development of improved tools for TB control.
5.2 (Malaria) There is also a critical need
for improved tools for malaria control, to prevent transmission
from mosquito to man, drugs to treat clinical infections and an
effective vaccine to prevent death and disease. Improved diagnostics
are also required particularly to identify active infection and
thereby facilitate appropriate drug use.
5.3 (AIDS) Any complete solution to the
problem of HIV/AIDS with involve either a treatment that cures
individuals from HIV-1 infection (eg drug therapy) or a simple
method to prevent virus transmission (eg vaccination). None exists
as yet.
5.4 (Flu) Better coordinated action to reduce
infection in poultry is required. Economic concerns need to be
addressed.
6.1 The main role of the MRC's National
Institute for Medical Research is in carrying out fundamental
research to understand the complex biology of these formidable
pathogens and to feed the translational pipeline that leads to
new tools for disease control. If we are to avoid repeating the
post-war failures in disease control, we have to develop a better
fundamental understanding of the process of infection and the
causation of disease in a multidisciplinary effort that includes
microbiology together with immunology and population biology.
This is being achieved in the research environment of NIMR, with
appropriate links to clinical and pharmaceutical partners.
6.2 (Flu) MRC has a 60 year old commitment
to WHO to support the World Influenza Centre at NIMR, which as
a WHO Collaborating Centre, has a key role in monitoring the evolution
of human influenza (and advising on vaccine composition) and detection
and identification of novel, potentially pandemic human influenza
infections.
7.1 (TB) International travel and immigration
are important influences on spread of TB. There is a need for
enhanced international surveillance; particularly to monitor the
spread of untreatable multidrug-resistant and extensively drug-resistant
strains.
7.2 (Malaria) Climatic changes such as rainfall
and changes in land use such as deforestation or drainage can
affect mosquito breeding and therefore the potential for the transmission
of malaria. Poverty and social disintegration, caused by wars
or civil strife can very quickly affect the effectiveness of control
programmes.
7.3 (AIDS and Flu) Poverty remains an important
consideration.
8. (TB) A total of 8497 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. While a large proportion of cases result
from transmission outside of the UK, periodic TB outbreaks in
schools and local communities highlight the risk of local spread.
Eliminating TB from the UK will depend on effective global control.
9. (TB) There are four limitations facing
TB control efforts: (a) inefficient diagnosis means that active
cases are infectious for long periods before receiving treatment,
(b) treatment requires daily delivery of a combination of drugs
over a period of six months or more; resulting in problems of
drug delivery and patient compliance, (c) selection and transmission
of untreatable drug-resistant strains as a result of inefficient
treatment, and (d) dramatically enhanced progression to active
disease in individuals coinfected with HIV. There is no single
mechanism to address all the issues. We need to develop better
diagnostics, novel drugs that act more quickly, and new effective
vaccines. Development of these tools is limited by a lack of understanding
of the fundamental underlying biology of the disease from the
causative microorganism to the host response.
10. (Malaria) There is no doubt that spraying
with residual insecticides such as DDT can have a substantial
effect on malaria transmission. The cessation of its use, together
with the absence of alternative control measures, has had a significant
effect on the spread of the disease.
11. (Flu) 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. Better responses to
calls for sharing of benefits would achieve more effective international
cooperation.
12.1 (TB) Currently, the incidence of drug-resistant
TB is high in Eastern Europe (perhaps 10-20% of total cases).
In most parts of the world, drug-resistant strains account for
less than 10% of total cases. Spread of multidrug-resistant and
extensively drug-resistant strains presents a major future threat
to TB control. Development of tools to identify highly-transmissible
resistant strains needs more research.
12.2 (Malaria) Resistance to chloroquine,
once an effective and cheap drug of choice for malaria, and to
other drugs such as Fansidar®, has had very substantial effect
on the impact of malaria. Cheap and effective new drugs and combinations
are urgently required since in the near future we are going to
be largely reliant on expensive artemisinin-based combination
therapies (ACTs), to which resistance will undoubtedly develop.
12.3 (AIDS) The importance of drug resistant
HIV transmission is unclear and requires further investigation
12.4 (Flu) Not currently an important factor
in the case of avian flu. Of enormous potential importance if
transmission of drug-resistant virus to humans occurs.
13. No response.
14.1 (TB) Research funding from the Bill
& Melinda Gates Foundation has a positive influence in insisting
on "global access" for all new medicines.
14.2 (Malaria) Not an important consideration.
14.3 (AIDS) Clearly there are tensions between
the IP/profit concerns of the pharmaceutical industry and the
health needs of economically disadvantaged nations and these have
impacted the flow of medicines. These tensions will continue in
the future unless extended agreements can be negotiated.
14.4 (Flu) 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.
15.1 (TB and malaria) There are good interactions
between research laboratories in the EU and the US. Interactions
with laboratories in endemic countries vary in quality. There
is a particular need for robust surveillance systems to monitor
transmission of drug-resistant TB between eastern and western
Europe.
15.2 (Flu) Much has and is being done in
relation to influenza and pandemic planning. WHO has taken an
important lead in many areas.
16. (Flu) These regulations seem to have
omitted an essential requirement: the provision of assistance
to developing countries in developing the capacities to fulfil
their obligations.
17. No response.
18.1 Cross-species transmission of an animal
virus into humans occurs on a regular basis. Fortunately person-to-person
virus transmission is rarely sustained. However the example of
HIV-1 tells us what can happen if an animal virus becomes established
in the human population. There is no inherent difference between
an animal and a human virus; funding bodies and governmental departments
should be discouraged from creating artificial distinctions in
research responses in this area.
18.2 (TB) 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.
19.1 (Flu) 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. While public health measures and translational
research are clearly urgent priorities for infection control,
development of effective new measures will depend on achieving
a better understanding of the complex biology that underlies infection,
immunity and progression to disease. There is still a major need
for research in this area.
17 January 2008
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