Examination of Witnesses (Questions 140
- 159)
MONDAY 25 FEBRUARY 2008
Professor Peter Borriello, Professor Mike Catchpole,
Professor Francis Drobniewski and Professor Peter Chiodini
Q140 Chairman:
And drug resistance?
Professor Borriello: Drug resistance has always
been with us. Of course it would not emerge as readily and become
as apparent until you had drugs you were using to kill the germs
with, almost by definition. Otherwise, nobody would be interested
in looking. There is increasing concern—I think rightly
so—that the spread of resistance between germs is now so
fluid and so capable, particularly multiply antibiotic resistance
capability, where increasingly we are learning that those bits
of the DNA that give resistance can be transferred as a block
with lots of different resistance in it, not just one at a time,
that it is causing people concern. The ability to create new classes
of antimicrobials that work in an entirely different way to regain
the upper hand becomes increasingly more difficult.
Q141 Chairman:
Do you foresee a particular problem on the HIV-TB one or not?
Professor Borriello: Of course, resistance is
a problem in both organisms and becoming an increasing problem.
One of the lessons we learned from antibiotic resistance in bacteria
was that you are better off giving more than one antimicrobial
at the same time, because that minimises the risk of one resistance
appearing and then the other one. In crude terms, you just bash
it hard and big. That has been quite successful for HIV so far
but of course there is resistance emergence.
Professor Catchpole: As I am sure Committee
members are aware, resistance to the HIV drugs that we have has
developed but the alarmingly rapid progress in the early stages
would seem to have been slowed at least by the use of multiple
therapies and it may well be that, as pharmaceutical advances
move on, we can add to that multiplicity. It remains a concern
but I think prompt action when it was recognised and the role
of surveillance in recognition are important. It has helped us
to perhaps slow down what we thought was looking like an alarmingly
rapid process in the early days.
Professor Drobniewski: For TB the situation
is perhaps more grim. Certainly we have seen a year-on-year increase
in the numbers of cases of multi-drug resistant tuberculosis,
globally which is a benchmark for the most severe form of drug
resistance in tuberculosis, and there are relatively few new drugs
under development. There have been a number of international initiatives
to try and bring new drugs to market and some of them are reasonably
successful. It is very safe to say that the numbers of drugs are
relatively small, particularly in terms of new classes which were
mentioned earlier on, so we are seeing high rates of multi-drug
resistance, particularly in Eastern Europe for example, and also
in parts of China and parts of India.
Q142 Chairman:
Although it has to have an understanding of the diseases concerned,
this Committee's primary focus is on the Intergovernmental Organisations
and the way the UK Government can work through them. Do you think
either the World Health Organisation or the Intergovernmental
Organisations could make any changes in the way they are working
at the moment in order to deal with the problems that you have
just been talking about?
Professor Borriello: There may be a need for
more interaction on accepting common approaches to antimicrobial
prescribing. One of the things that is very different throughout
the world is antimicrobial prescribing as well as access to antimicrobials.
A number of countries have over-the-counter, unrestricted sales
and a number of countries do not. The hard evidence as to the
extent to which that difference in access contributes to the resistance
seen in those countries is not as readily available but some agreement
and discussion based on evidence that should be generated to better
inform prescribing practice could be useful at an intergovernmental
level because, just like germs now can travel easily on a human
host, so can their resistances.
Q143 Lord Avebury:
Which International Organisation should be doing that work?
Professor Borriello: From my understanding of
it, I would suspect the WHO would have an immediate mandate to
at least raise the issue and try to convene such meetings through
its Regional Offices.
Professor Drobniewski: Certainly the WHO has
taken a significant initiative in addressing multi-drug-resistant
tuberculosis, speaking specifically on that. For example, a global
task force was called about a year and a half ago and that created
a blueprint for further activities and action that were needed.
This was a mix of strategic implementation but also technical
implementation and technical requirements that were felt essential
to achieve the strategic goals. For example, the ability to diagnose
drug resistance much earlier was considered to be something of
great importance. The WHO certainly has taken a lead along with
other organisations: for example, the Foundation for Innovative
and New Diagnostics, which is based in Geneva and has a close
relationship with the WHO and in terms of new drug developments,
the Global Drug Alliance, based in New York and, more broadly
in terms of new TB vaccines, the AERAS Foundation. Certainly there
has been a broad, strategic examination and leadership from the
WHO in that area.
Professor Chiodini: I wonder if I can add a
little bit on antimalarial drug resistance because this is the
single biggest factor in the severe malaria situation which we
face at the moment.
The Committee suspended from 4.25pm to 4.35pm
for a division in the House
Drug resistance is a major factor in the deteriorating
malaria situation. We lost Chloroquine in the Far East in the
1970s, in Africa through the eighties, which was associated with
increased child mortality as treatments were failing and now it
is effectively useless in sub-Saharan Africa. Similarly, sulfadoxine
pyrimethamine is essentially unhelpful in that area, so the WHO
is moving now to combination therapies. We have few drugs coming
through the pipeline and that creates a big issue for us. There
are some useful Public Private Partnerships, and indeed Baroness
Chalker from this House chairs the Medicines for Malaria venture.
I am sure you will be speaking to her about it later in the course
of this. That is an example of an excellent Public Private Partnership.
It is fair to say that even with that the need for new drugs to
come through when the current treatments fail, as all treatments
eventually do with malaria I am afraid, is an imperative.
Q144 Chairman:
They all fail eventually?
Professor Chiodini: The parasite that causes
fatalities from cerebral malaria or severe anaemia in children
is very adept at becoming drug resistant. Once it has become resistant
to one drug, its ability to become resistant to others seems to
be more rapid. For example, in South East Asia after Chloroquine
we had multi-drug resistant malaria. All we were left with at
that time was Quinine. SP (Sulfadoxine plus Pyrimethamine) and
Chloroquine had essentially gone. There are already reports of
possible resistance to the Artemisinins and those await confirmation,
but it is unfortunately a fact of malariology that eventually
drugs do fail and we have to be prepared for that and have other
drugs in the pipeline. It would be a shame if what is currently
an excellent treatment giving dramatically good results were to
lull us into a false sense of security. We need a continuing pipeline
of drugs to back that up.
Q145 Chairman:
If you think of any further ways in which the WHO or the Intergovernmental
Organisations can address the concerns you have raised, please
let us know.
Professor Catchpole: Can I add a thought on
the role of the European Commission? I was at a meeting of the
European Centre for Disease Control, which I know we are going
to talk about, at their Advisory Forum last week with the representative
of the European Commission, DG Sanco. It was mentioned that antimicrobial
resistance has been flagged up at a meeting of the three countries
that have the next three Presidencies. They have all indicated
a particular interest in antimicrobial resistance as a public
health issue. That does present an interesting and exciting opportunity
because the Commission, of course, has competences and responsibilities
not only in the area of health but also in terms of industry.
That is what we need to tackle. This problem is where health and
industry are working together.
Q146 Lord Howarth of Newport:
Professor Chiodini, whose responsibility is it? Where does responsibility
lie for commissioning the next generation of drugs, for ensuring
that that research and development occurs?
Professor Chiodini: It is a very good point
because, unlike, if one were looking at a Cholesterol-lowering
drug for example, the market for antimalarials is overwhelmingly
in the Tropics, where there is little money to pay for the drugs.
Thus, for a pharmaceutical company looking at the product they
want to develop, an antimalarial would not be a big money-spinner
for it. There is some money to be made from antimalarial prophylactic
drugs but, again, that market is not enormous compared, say, to
Cardiovascular drugs. Thus, I think this is one area where intergovernmental
cooperation combined with the WHO should be involved in the kind
of public private partnership that I have mentioned, so that funding
can be put in to make it more attractive for manufacturers to
produce drugs. At the same time, we already have good examples
of the pharmaceutical industry donating drugs, for example for
filariasis control. Thus, with some imaginative funding up front
to get the thing running, developed and then put through the various
clinical trials, thereafter there is an element of pro bono
that one might hope for from industry in there. I do not think
they are ever going to make very big money out of antimalarials,
so there will always have to be some incentive for that.
Q147 Lord Howarth of Newport:
I think you are saying to us that, with the present structure,
that decision is not going to be taken. It is not foreseeably
going to happen. Is that correct? If so, how do you think structures
should be reformed to ensure that a new generation of antimalarial
drugs is developed?
Professor Chiodini: I think the situation is
now much better. I did mention the Medicines for Malaria venture,
which is hoping to get a new antimalarial out by 2010. It is with
that kind of model that I think the compounds can come through.
There are many basic scientists looking at antimalarial chemotherapy
and plenty of promising new compounds, and the mechanisms through
public-private partnerships do exist. I think they could do with
more support. Everybody makes a plea for funding but until very
recently malaria has always been very much a poor relation and
yet more needs to be put into that.
Q148 Chairman:
Professor Catchpole, you led us on rather neatly to the European
Centre for Disease Prevention and Control. I note you are a member
of it and I note also that the evidence from the HPA is quite
critical of this organisation. I know it is fairly new but I would
be grateful if you could spell out what that criticism is. What
is the link between the ECDC and the WHO. Is it good? Is it bad
or is it just not functioning? Is it not built up yet? It is hard
to get a picture from what you are saying as to how this is working
or whether it just needs time.
Professor Catchpole: Just to provide a little
context to our response, which I think very much focused on the
"areas for improvement" question that was put to us,
the important thing is that the response is paraphrased in the
"likely areas of questioning" paper: "... ECDC
has yet to demonstrate any added value ...". The point we
were making is that in one of the areas of ECDC's activities,
which is surveillance, there have been some issues. I will come
back to those but I think it is important to make the point that
ECDC has delivered added value in some of its other areas of work.
For example, in the provision of scientific advice, it did a very
good job of summarising the evidence for the effectiveness of
the many different interventions that we might need to look to
to deal with pandemic influenza. It has done a lot of work in
developing training to improve the capacity of some of the newer
Member States in their epidemiological response capacity. It has
also done a lot in terms of improving some of the communication
processes we have by managing information systems. But in the
area of surveillance ECDC was not created in a vacuum. For the
last two decades there have been a number of European-wide surveillance
collaborations largely funded by the European Commission for diseases
such as Legionnaire's Disease and Salmonella. Those have provided
a lot of added European value over the years. With the creation
of ECDC, the strategy is to move the coordination function for
those surveillance initiatives from the host institutes which
are based around Europe—some of them were hosted by the
Health Protection Agency—to Stockholm. In a way, it is a
tall order to ask ECDC to provide additional added value for networks
that were already there. ECDC's main challenge is to improve the
standard of all those surveillance networks. What they have yet
to do is bring up all surveillance networks to the same standard.
Q149 Chairman:
Your criticism is that this is work in process but they have not
demonstrated they have done it yet. Is that right? Or are you
saying that they have not quite got their act together and thought
about it?
Professor Catchpole: They have clearly thought
about it. They have not yet got the systems and structures in
place. I think it has taken them longer than probably they had
anticipated to put some of those systems and structures in place.
You quite rightly picked up on a comment about degrading assessment
and response. There have been a couple of examples in the early
days of their establishment where we felt that we had to push
them on the response to, say, salmonella outbreaks, but I think
things are moving on. Just to put it in context, given the word
limits we had, we focused on the areas for improvement. In terms
of the interaction with the WHO, that is an interesting question.
I have been involved in a couple of joint exercises which involve
both the World Health Organisation European Office particularly
and ECDC, looking at how they would respond to an emergency, such
as a Viral Haemorrhagic Fever case coming back on an airliner
with people from all over Europe. They are running exercises together
which are helping flush out both the synergies and tensions between
the organisations, and there have been tensions. They are putting
in place shared surveillance activities, on, for example, TB with
HIV. There will be a single managed surveillance system, as there
has been, but that will be hosted in ECDC, collaboratively run
with the World Health Organisation European office. There are
clear examples of how they are working together.
Q150 Chairman:
Is that working at the international level of the WHO or the European
level?
Professor Catchpole: That is working at the
European level but ECDC, I believe, also has contributed to discussions
at the global level. For example, there has been a recent need
to review some of the procedures and protocols around dealing
with multi-resistant TB passengers on airlines. An area which
is clearly an area of unresolved tension, for want of a better
phrase, between the World Health Organisation and ECDC is the
area of the new International Health Regulations and the reporting
requirements that those place on all signatories, which include
ourselves, to report public health emergencies of international
concern to the World Health Organisation. At the moment, interestingly,
ECDC does not have access to the World Health Organisation's information
website where it displays all reports because ECDC have to be
a national Member State. They are not a recognised, legal, international
entity or something like that. It may be that with the passing
of a European declaration ECDC may then take on that mantle which
will allow them to have access. There is a line in the International
Health Regulations which was expressly put there so that the European
Commission and the European Union could potentially be a fully
signed up member of the international regulations. That is the
one important area where I see that there is still some tension
about whose role within Europe it is—whether it is the WHO
European Office's or the ECDC's role to deal with this.
Q151 Lord Geddes:
Professor Catchpole, an extremely direct question: on balance
and from a global perspective, would we be better off without
the ECDC?
Professor Catchpole: No.
Q152 Lord Geddes:
What is it contributing?
Professor Catchpole: Do you want me to answer
that purely from a UK perspective? What it is contributing for
us is that it facilitates considerably our ability to communicate
with colleagues around Europe, particularly the newer Member States
and the Baltic states, where for example we not too long ago had
a case of an individual from this country who unfortunately died
of an infectious disease in one of the Baltic states. We needed
to undertake a risk assessment where they acquired their infection,
in this country or in the Baltic state, and who would need to
be offered appropriate prophylaxis and treatment. ECDC greatly
facilitated making sure that we could communicate with them, putting
us in contact with the right people. If we had an issue about
not getting a response, they pushed on that. From a UK perspective,
that is one small example. There are others. More broadly from
a European Union perspective, if you put that question to someone
from one of the smaller states in Europe they would say they absolutely
feel that the get huge value from knowing that ECDC is there.
We are fortunate in this country. We have a tremendous resource
of experts and expertise that can provide us with information
and advice on how to deal with SARS or other emerging problems.
They do not have that expertise and depth in other parts of Europe.
Q153 Chairman:
Including the Euro Office of the WHO? Lord Geddes, in a sense,
is right. Why two? Why ECDC and the WHO Euro?
Professor Catchpole: If you compare ECDC to
the WHO's European office, ECDC has more resources in some areas,
particularly in terms of its ability to provide resources on infectious
disease issues, than are available in the WHO European office.
It provides additional capacity and competence and it provides
additional capacity and confidence in areas where it is needed.
Q154 Lord Avebury:
I have a question about RASBICHAT, which is mentioned as providing
an early alerting capability between Member States of the European
Union. Does that belong to ECDC? Or is it entirely separate from
it?
Professor Catchpole: It belongs to the Commission.
Even the system that is operated by ECDC for communication on
purely infectious disease issues, although it is technically managed
by ECDC, is owned by the Commission. It is formally the system
for the Commission to communicate with Member States and for Member
States to communicate with each other. All of these systems are
owned by the Commission.
Q155 Lord Avebury:
Similarly to Lord Geddes's question, I wonder why we need to have
RASBICHAT, when you say it is a similar system to the Global Health
Security Initiative. Surely there ought to be one worldwide system
for early alerting of incidents which may lead to serious infectious
diseases spreading?
Professor Catchpole: We agree with that.
Q156 Lord Avebury:
You do not think there is a need for these two organisations?
Professor Catchpole: I agree it is helpful to
have a common communication system but what then follows on in
terms of the risk assessment, the provision of expert advice,
the coordination of response may not mean that it is just one
organisation.
Q157 Lord Avebury:
Are you talking about IT systems in these two acronyms here?
Professor Catchpole: Yes.
Q158 Lord Avebury:
Do the IT systems have common protocols?
Professor Catchpole: They do not at the moment.
Q159 Lord Avebury:
How appalling.
Professor Catchpole: There has been a lot of
discussion about the system that the European Commission and ECDC
operate called EWRS, Early Warning and Response System and about
countries like ours being able to use that to report to the WHO
under the International Health Regulations. The WHO have said
they are prepared to receive reports in that way but all further
communication under the International Health Regulations requirements
they would not make through that system. They would choose to
communicate back to the Member States through a different system.
Professor Borriello: I feel quite strongly that
there is an intergovernmental role in looking at all the different
early warning and response systems that exist and also their interoperability.
There are some cases where there do need to be some separate systems
and more dedicated, different access because the customer base
may be different. For the ones on security and bio-terrorist response,
they would need a particular group of users and reporting lines
and also each of the nation states would wish certain offices
to be alerted and not others, for example. There are also the
food ones. They have been set up. Even within Europe there are
food alerting systems which are not the same. If you have a food-borne
outbreak and there is Salmonella in food affecting multiple countries,
as a focal point both the International Health Regulations and
the EWRS, which is the role the HPA plays for the UK, do we go
to EWRS and then IHR? Or do we go to both? Is there such a circumstance
when it would only be one and not the other? Whose role is it
to alert the food alerting systems if it is a food-borne pathogen?
One can see why these systems arose. Although there is some complication,
it is important to remember that we are in a much stronger position
now than we were to the extent that in the early days you needed
some refining to take the noise out of the system.
Chairman: I have picked up from elsewhere that
there is a concern about the international surveillance system
and some restructuring needed. If you want to give some thought
to that, as to what sort of organisation would be required, we
will be taking evidence on that on a further date down the line.
If you have any views, I would like the Committee to see them.
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