Memorandum by the Malaria Centre, London
School of Hygiene & Tropical Medicine (LSHTM)
These comments are restricted to points about
malaria specifically and in answer to the specific questions posed
by the Committee; the LSHTM is responding more generally to the
Committee across the 4 diseases and this acts as a malaria-specific
annexe to that response.
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. Experience has shown that where nothing
else changes the overall burden of malaria decreases as economic
status improves. This process is now taking place for malaria
in many, but by no means all, parts of Asia. However, in Africa
malaria remains a major burden and whilst there is early evidence
it may be decreasing in some areas it remains very common. Deaths
from malaria increased in some areas over the last decade- this
was probably linked to increasing drug resistance.
2. What reliable data exist regarding the
numbers of people infected globally with the four diseases[30]
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. Generally accepted WHO estimates are
300-500 clinical cases of malaria and more than 1 million malaria
related deaths per year, 80-90% of these being in tropical Africa,
although there are many important areas of the world where the
transmission rates are not much better than an educated guess.
In highly endemic areas of tropical Africa there are many more
than 500 million infections acquired per year, but many of these
are more or less symptomless infections of older people who have
acquired a considerable degree of immunity in response to repeated
infections in childhood. Recently there has been much more funding
for malaria control from the Global Fund for AIDS, TB and Malaria
(GFATM) and other donors and in the last 12 months the GFATM has
provided 46 million long lasting insecticidal nets to several
African countries. Furthermore, indoor spraying with residual
insecticides is being revived and modern more effective (and more
expensive) anti-malaria drugs are being made available.
In the UK and other developed countries malaria
transmission was eliminated in the first 60 years of the 20th
century. However Anopheles mosquitoes (of a different sub-genus
from those in Africa) still exist in developed countries and potentially
can pick up malaria parasites; very occasional transmission has
been reported in Italy from imported infections. In the UK there
are about 1,750 malaria cases a year, but all are imported in
people who have recently travelled in the tropics and acquired
their infections there.
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. If current levels of funding from donors
are sustained or increased for insecticidal nets, indoor residual
spraying, anti-malaria drugs and support for health services,
further reductions in the burden of malaria can be expected. However,
there are no grounds for complacency; previous reductions have
been followed by rebound when control measures were relaxed. Recent
progress could be reversed if spreading occurs of recently detected
genes for resistance to pyrethroid insecticides or Artemisinin
based anti-malaria drugs. Existing efforts to develop replacement
compounds need to be re-inforced. The continuing reduction of
falciparum malaria in Asia will probably continue as areas industrialise.
Malaria has reinvaded areas (such as in Central Asia) where complex
emergencies have had an impact on control measures.
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. Until recently the principle blockage
was inadequate resources to deploy tools known to be effective
at preventing and treating malaria. This is still a problem, but
currently a declining one; the Bill and Melinda Gates Foundation,
WHO and the Roll Back Malaria partnership have all committed to
the elimination of malaria—a challenging goal. Other major
doors, such as the Clinton Foundation, which have not worked previously
on malaria are now entering the field and there are many new smaller,
NGOs being established to support malaria control (eg. UK Coalition
on Malaria, European Coalition on Malaria etc). It is essential
that a realistic roadmap for the elimination of malaria is devised
and that all major groups can support.
The major current blockage in much of Africa
are the very weak health systems and services. Most of those who
have malaria do not reach the formal healthcare sector, those
that do are often misdiagnosed or treated with inadequate drugs.
Current bednet distribution systems only reach a fraction of those
who need them in many highly endemic countries. Effective tools
to prevent and treat malaria are therefore not getting to those
who need them even where the resources to provide them are there.
Reversing this will require significant and long-term investment
in health systems, which are seldom donor priorities.
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. The LSHTM Malaria Centre has over 70
scientists for disciplines ranging from basic science through
clinical research to social science and economics whose main interests
are malaria who work in a multidisciplinary way. This is probably
the largest scientific malaria grouping worldwide. In addition
to research LSHTM staff provide technical advice on malaria to
DFID, DH, WHO and NGOs as well as technical agencies in endemic
countries. LSHTM also has an important training role providing
masters and doctoral level training for many developing country
scientists and control programme managers who are playing a critical
role in malaria control in their own countries.
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. (a) Global warming: if an
Anopheles mosquito picks up malaria parasites by biting
an infected person, the development of the parasites to the stage
at which they can be passed on during another bite is highly temperature
dependent. African Anopheles populations are larger where
temperatures are higher, provided that there is enough rain to
produce clean surface water in which their larvae can survive.
In African mountains Anopheles populations and malaria
incidence decrease progressively from high levels in the warm
lowlands to almost zero at 1,700 metres where it is much cooler.
If there is substantial global warming it is reasonable to expect
the upper altitude limit for malaria transmission to rise. However,
the Inter-governmental Panel on Climate Change (IPCC) has recently
stated that there is no convincing evidence that such a change
has occurred yet.
The impact in Europe is however likely to be
limited or nil provided effective heath systems remain in place.
After eradication of malaria transmission in Italy in 1962, Anopheles
populations continue to exist but since that time there have
been only about five cases of malaria which are not readily explained
as imported cases in travellers who have been in the tropics.
Italian summers are hotter now than the most extreme predictions
for climate change in the UK. This indicates that, with an effective
and equitable West European health service, almost all imported
malaria cases are promptly and effectively treated before a local
Anopheles mosquito could be infected if it bit the person
concerned. The HPA Malaria Reference Laboratory (part of the Malaria
Centre) provides surveillance for the UK.
(b) Poverty: Poverty and malaria
constitute a vicious circle. It has been estimated that up to
15% of some African countries GDP is lost to malaria, and whilst
the data on which this is based should be treated with caution
it certainly takes a major economic toll on development. At an
individual level malaria increases poverty by many routes, including:
(i) in the wet (growing) season, when farmers have most work to
do, they are often incapacitated by malaria, the incidence of
which peaks in the wet season when Anopheles breed in largest
numbers and (ii) children are often kept away from school by malaria
attacks.
The poorest suffer most of the effects of malaria,
being more likely to acquire the disease, and more likely to die
from it if they get it. They tend to live closest to mosquito
breeding sites and be least protected by malaria control programmes.
They are least able to buy effective protection (such as insecticide
treated bednets), or to buy effective antimalarials which are
only provided free in some countries. Currently most countries
rely on user fees for healthcare. Indirect costs of seeking healthcare
are also a major barrier, and the poorest often get most of their
care from shops where advice is often poor. Free bednet distribution
only occurs in a minority of settings.
(c) Population movement: The current
mass movement of rural Africans into urban slums will have many
adverse effects, but it may actually reduce malaria incidence
as the polluted surface water in urban slums is only suitable
for the breeding of Culex mosquitoes, not Anopheles
which are the only vectors of human malaria.
(d) International travel: Increased
inter-continental travel will increase the number of people from
countries which now have no malaria transmission, such as the
UK, who need to be warned to take anti-mosquito and drug prophylactic
precautions while in the tropics. International travel makes the
spread of drug resistant malaria, once it starts, rapid and inevitable,
and will complicate efforts to eliminate malaria in some geographical
regions whilst it continues in others.
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?
10. In the preamble to the Stockholm Convention
on Persistent Organic Pollutants, there is mention of the desirability
of replacing DDT house spraying against malaria mosquitoes by
equally effective and affordable alternatives, if and when these
become available. However, there is a detailed amendment in the
Convention which specifically authorises continued indoor use
DDT against disease vectors using W.H.O. approved methods. The
amendment accepts that outdoor use of DDT against agricultural
pests should be banned because of the evidence that DDT break
down products can enter the outdoor food chain and cause harm
to attractive wildlife such as peregrine falcons. In the final
round of negotiations about the Convention in 2000, the amendment
was introduced by the South African delegation and the wording
was subject to detailed negotiation by contact groups. When finally
brought to the plenary negotiating session, the amendment was
accepted nem.con. by the 150 United Nations delegations
present.
The South Africans were motivated to introduce
this amendment because their own anti-malaria spraying programme
was facing a serious problem. After 50 years of successful use
of DDT from 1945 to 1995 they had yielded to environmentalist
pressure and switched from DDT to pyrethroid spraying. Within
four years, one of the two important malaria transmitting species
in southern Africa, Anopheles funestus, was found to have
evolved resistance to pyrethroids, but not DDT, and incidence
of malaria cases had increased by four fold. Fortified by the
existence in the Convention of the amendment which they had introduced,
the South Africans switched back to DDT spraying in 2001. The
next year they switched to Artemisinin Combination Therapy as
first line anti-malaria drug. By 2004 incidence of malaria had
declined by 91% compared to the peak year in 2001 (Maharaj et
al, 2005). With South African assistance parts of Zambia and
Mozambique have successfully taken up indoor spraying with DDT
against malaria mosquitoes.
There have been numerous published reviews of
the evidence about possible adverse effects of DDT on human health.
Most show no convincing evidence of such adverse effects, but
there is evidence of an association between level of DDT break
down products in sera of American women in the 1950s-60s and probability
of them having pre-term births (Longnecker et al, 2001). However
detailed data were collected by Giglioli (1972) on maternal and
infant survival and the birth rate in Guyana in the 1930s (before
availability of DDT), the 1940s (during its intensive indoor use
against malaria mosquitoes) and in the 1950s (after malaria eradication
had been temporarily achieved). The data show remarkable and progressive
improvements in maternal and infant survival and live birth rate
over those three decades which indicates that, if it is true that
DDT causes an increase in premature births, the beneficial effect
of DDT used to eradicate malaria far outweighs any adverse effects.
Where there is resistance in malaria mosquitoes
to pyrethoids but not DDT, as was found in South Africa, there
is clearly a strong argument to continue to, or to switch back
to, spraying DDT. However, where (as is often the case) there
is no resistance of this type, the argument for using DDT is that
the cost per house sprayed per year is somewhat less than it would
be for using a pyrethroid. This cost difference is now not very
large. Some donors are concerned about use of DDT and are willing
to donate a larger sum to allow a pyrethroid to be used to protect
the same number of houses. It is surely better that they do so
rather than delay start of a spraying project while wrangles continue
about which insecticide to use.
REFERENCES
Giglioli (1972) Bull WHO 46: 181-202.
Longnecker (2001) Lancet 358: 110-114. Maharaj et
al (2005) S Af Med J 95: 871-4.
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. There is clear evidence that part of
the recent deterioration in the global malaria situation, especially
in Africa, was due to the emergence of resistance to chloroquine
and sulphadoxine pyrimethamine (SP). Unfortunately, the malaria
community was slow to pick up on the advantages of combination
therapy in the prevention of the emergence of resistance. This
lesson has now been painfully learnt and it is likely that in
future antimalarials will, as in the case of tuberculosis and
HIV, almost always be deployed as combination therapy. This should
delay the emergence of drug resistance but will not prevent it.
Thus, it is essential that research continues to develop new classes
of antimalarials even at a time when there does not seem to be
an urgent need, as is the case at the moment when high levels
of success are being achieved with artemisinin combination therapy
(ACTs). It is important that groups such as the Medicines for
Malaria Venture, which are developing new drugs continue to receive
support.
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?
14. For malaria there is a small but real
time-lag and increase in costs associated with the fact that drugs
have to be registered separately in each country. A pan-African,
or regional (eg SADEC) recognition of drug licensing would be
helpful.
On an IP related issue, the penetration of fake
(useless) antimalarials into the market is a very worrying development
which may lead to many avoidable deaths. These are very sophisticated
fakes generally imported into the end-country, and this requires
rapid international action by governments. In parts of Laos 80%
of all antimalarials sold are fake. However, in Thailand the problem
has been largely avoided to date by making the sale of antimalarials
illegal and providing them free of charge through a widespread
network of government health centres, backed up by quality control
of supplies.
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. For malaria the main issue is detecting
the spread of drug resistance and insecticide resistance. Various
resistance detection networks have been set up to do this, often
with starter funding from donors (including DFID) but securing
funding for these to continue has proved very difficult. Research
funders say this is the proper job of government, and governments
do not see this as a priority. As a result almost all have collapsed.
Resistance monitoring therefore depends on ad-hoc groups of research
groups—which means that large parts of Africa and Asia have
no data on drug or insecticide resistance at all, and public health
planning occurs only when resistance has reached crisis levels.
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. It is unlikely the IHR, either old or
new, will be relevant to malaria.
16 January 2008
30 HIV/AIDS, Tuberculosis, Malaria and Avian Influenza. Back
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