Who Expert Committee On Malaria: Twentieth Report
Who Expert Committee On Malaria: Twentieth Report
Who Expert Committee On Malaria: Twentieth Report
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Twentieth Report
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Twentieth Report
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WHO Library Cataloguing-in-Publication Data
WHO Expert Committee on Malaria (1998 : Geneva, Switzerland)
WHO Expert Committee on Malaria : twentieth report.
(WHO technical report series ; 892)
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Contents
1. Introduction 1
5. Disease management 16
5.1 Management of uncomplicated malaria 17
5.1.1 Diagnosis 18
5.1.2 Availability and quality of treatment 24
5.2 Management of severe malaria at the periphery 25
8. Prevention of malaria 37
8.1 Selective vector control 37
8.1.1 Indoor residual spraying 38
8.1.2 Use of DDT in malaria control 38
8.1.3 Use of insecticide-treated materials 39
8.1.4 Management of malaria in development projects 40
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8.1.5 New developments in Africa 41
8.1.6 Use of gametocytocidal drugs 42
8.2 Chemoprophylaxis 42
8.2.1 Chemoprophylaxis among non-immune people visiting
endemic areas 42
8.2.2 Prevention of malaria in pregnancy 42
8.3 Malaria vaccines and basic research 44
8.4 Trends in insecticide resistance 44
8.5 Costeffectiveness of preventive measures 46
Acknowledgements 64
References 65
Annex 1
Use of DDT in vector control 69
Annex 2
Improving information exchange 71
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WHO Expert Committee on Malaria
Geneva, 1927 October 1998
Members
Dr R.B. Biritwum, Professor, Department of Community Health, Ghana Medical
School, Accra, Ghana
Dr B.M. Greenwood, Professor, Department of Medical Parasitology, London
School of Hygiene and Tropical Medicine, London, England
Dr P.F. Guillet, Head, Laboratory of Insect Pests, Institute for Research and Devel-
opment, Montpellier, France
Dr Krongthong Thimasarn, Director, Malaria Division, Department of Communi-
cable Disease Control, Ministry of Public Health, Nonthaburi, Thailand (Vice-
Chairman)
Dr K. Marsh, Professor, Kenya Medical Research Institute (KEMRI) Centre for
Geographic Medicine Research Coast, Kilifi, Kenya (Rapporteur)
Dr K.M. Paluku, Director, Programme for Control of Communicable Diseases in
Children, Kinshasa, Democratic Republic of the Congo
Dr T.K. Ruebush II, Chief, Malaria Epidemiology Section, Division of Parasitic
Disease, Centers for Disease Control and Prevention, Atlanta, GA, USA
Dr W.H. Wernsdorfer, Professor, Institute of Specific Prophylaxis and Tropical
Medicine, University of Vienna, Vienna, Austria (Chairman)
Secretariat
Mr Tarekegn Abose, Manager, Malaria and Other Vector-Borne Diseases Control,
Ministry of Health, Addis Ababa, Ethiopia (Temporary Adviser)
Dr G. Barnish, Reader, Liverpool School of Tropical Medicine, Liverpool, England
(Temporary Adviser)
Dr Le Dinh Cong, Director, Institute of Malariology, Parasitology and Entomology,
Ministry of Health, Hanoi, Viet Nam (Temporary Adviser)
Dr A.L. El Idrissi, National Programme Manager, Department of Parasitic Diseases,
Ministry of Health, Rabat, Morocco (Temporary Adviser)
Dr A.V. Kondrachine, Chief, Malaria Control, Division of Control of Tropical
Diseases, WHO, Geneva, Switzerland (Secretary)
Dr Shiv Lal, Director, National Malaria Eradication Programme, Delhi, India
(Temporary Adviser)
Dr J.A. Najera, Crans-prs-Cligny, Vaud, Switzerland (Temporary Adviser)
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1. Introduction
The WHO Expert Committee on Malaria met in Geneva from 19 to
27 October 1998. The meeting was opened on behalf of the Director-
General by Dr D.L. Heymann, Executive Director of the Communi-
cable Diseases cluster. After describing the new organizational
structure of WHO which was to be implemented in late 1998, he
pointed out that during the last decade, considerable progress had
been made in malaria control worldwide.
He noted that the previous meeting of the Expert Committee, held in
1989, was an important milestone in elaborating worldwide guidance
for malaria control at a time when the global malaria situation was
seriously deteriorating. Most of Africa, south of the Sahara, contin-
ued to face an increasingly serious public health crisis as a result of the
disease. Numerous civil wars and social unrest in various African
countries, combined with fluctuating meteorological and ecological
changes favourable to malaria transmission in areas that were previ-
ously malaria-free, also contributed to the problem. This was exacer-
bated by limited national financial resources, the absence of external
support, inadequacies in technical guidance and insufficient experi-
ence in controlling malaria in highly endemic areas. The emergence
and spread of chloroquine-resistant Plasmodium falciparum further
aggravated the situation.
Although malaria occurred mainly in Africa, south of the Sahara, the
spread of multidrug-resistant P. falciparum which had developed
in frontier areas in south-east Asia and South America during the
1980s threatened malaria control in other parts of the world.
In view of this serious situation, WHOs Executive Board in 1990
proposed that a Ministerial Conference on Malaria be held to encour-
age affected countries and the international community to intensify
efforts to control the disease. After preparatory meetings involving
representatives of donor agencies, research institutions, the United
Nations and its specialized agencies, as well as managers, scientists
and administrators, a consensus was reached on current standards for
malaria control and a Global Malaria Control Strategy was formu-
lated (1). The Global Strategy was presented to and endorsed by the
Ministerial Conference on Malaria, which was held in Amsterdam,
Netherlands, in October 1992.
In 1993, the Economic and Social Council of the United Nations
initiated a review of the global malaria situation. This review was
conducted in response to concerns expressed by members of the
Council, especially those from countries in Africa where malaria was
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not receiving the urgent attention required from individual countries
and the United Nations system. The Councils review led to the
endorsement of the Global Strategy in the forty-ninth session of the
United Nations General Assembly in December 1994. The General
Assembly requested WHO to continue acting as the leading organiza-
tion for malaria control, and to develop an action plan (for 1995 to 2000)
in consultation with other United Nations agencies, other partners in
malaria control and the affected countries. The Economic and Social
Council of the United Nations endorsed the Action Plan in 1995 and
called for increased resources for the prevention and control of malaria.
A further important development occurred in March 1996 when ma-
laria was identified as a priority component of the United Nations
system-wide Special Initiative on Africa. In June 1997, the Assembly
of the Heads of State and Governments of the Organization of
African Unity (OAU) adopted the Harare Declaration on Malaria
Prevention and Control in the Context of African Economic Recov-
ery and Development, pledging to consider malaria control as a
priority. The Assembly reaffirmed its endorsement of the Global
Malaria Control Strategy and the actions of WHO in its implementa-
tion, and called upon Member States to give full political support to
malaria control, to develop and implement plans of action for malaria
prevention and control, and to ensure well coordinated multisectoral
action.
More recently, a Multilateral Initiative on Malaria in Africa (MIM)
has been established, which is particularly concerned with strengthen-
ing research capability in Africa. This Initiative followed meetings in
Senegal and the Netherlands in 1997 involving WHO, the World
Bank, other United Nations agencies, the European Commission, the
National Institutes of Health (the United States), the Wellcome Trust
(the United Kingdom), and other donors as well as research workers
from Africa and developed countries.
One of the most significant recent financial investments in malaria
control, particularly in Africa, south of the Sahara, was the allocation
of substantial funds by the Director-General of WHO to priority
countries for 1997 and 1998. In 1998, the newly elected Director-
General of WHO initiated the Roll Back Malaria project, thus estab-
lishing malaria as one of WHOs highest priorities.
The importance of malaria was also recognized by the members of the
Group of Eight Summit held in 1998 in Birmingham, England, at
which the British Government pledged 60 million towards the fight
against malaria. A significant proportion of this money will be allo-
cated to Roll Back Malaria.
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2. Current global malaria situation
At present, about 100 countries or territories in the world are consid-
ered malarious, almost half of which are in Africa, south of the Sahara
(Fig. 1). Although this number is considerably less than it was in the
mid-1950s (140 countries or territories), more than 2400 million of the
worlds population are still at risk.
The incidence of malaria worldwide is estimated to be 300500
million clinical cases each year, with about 90% of these occurring
in Africa, south of the Sahara mostly caused by P. falciparum.
Malaria1 is thought to kill between 1.1 and 2.7 million people world-
wide each year, of whom about 1 million are children under the age of
5 years in Africa, south of the Sahara. These childhood deaths, result-
ing mainly from cerebral malaria and anaemia, constitute nearly 25%
of child mortality in Africa. Fatality rates of 1030% have been re-
ported among children referred to hospital with severe malaria, al-
though these rates are even higher in rural and remote areas where
patients have restricted access to adequate treatment. Deaths from
malaria in countries outside Africa, south of the Sahara, occur princi-
pally in non-immune people who become infected with P. falciparum
in areas where diagnosis and treatment are not available.
One of the greatest challenges facing malaria control worldwide is the
spread and intensification of parasite resistance to antimalarial drugs.
The limited number of such drugs has led to increasing difficulties in
the development of antimalarial drug policies and adequate disease
management.
Resistance of P. falciparum to chloroquine is now common in practi-
cally all malaria-endemic countries of Africa (Fig. 2), especially in
east Africa, thus posing increasing problems for the provision of
suitable treatment. As a consequence Malawi and Kenya, in 1993 and
1996 respectively, changed their recommendations for first-line treat-
ment of uncomplicated malaria from chloroquine to sulfadoxine/pyri-
methamine, and Botswana and South Africa revised their treatment
guidelines in 1997. Resistance to sulfadoxine/pyrimethamine, the
main alternative to chloroquine, is widespread in south-east Asia and
South America. Recent reports from Kenya and the United Republic
of Tanzania suggest that changes in parasite susceptibility to
sulfadoxine/pyrimethamine have occurred and may presage clinical
resistance. Mefloquine resistance is now common in the border areas
of Thailand with Cambodia and Myanmar. Parasite sensitivity to
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Either alone or in combination with other diseases.
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Figure 1
Global malaria status
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Figure 2
Reported P. falciparum drug resistance
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quinine is declining in several other countries of south-east Asia and
in the Amazon region, where it has been used in combination with
tetracycline for the treatment of uncomplicated malaria. Conse-
quently, artemisinin and its derivatives are now increasingly being
used as first-line treatment in some of these areas.
Resistance of P. vivax to chloroquine has now been reported from
Indonesia (Irian Jaya), Myanmar, Papua New Guinea and Vanuatu.
Cross-resistance to amodiaquine sometimes occurs.
An increasing number of malaria epidemics have been recently docu-
mented throughout the world, particularly in Africa. Areas become
epidemic when conditions that normally limit transmission change
radically as a result of abnormally heavy rains, long periods of in-
creased humidity and temperature, or more permanent changes of
microclimate due to the development of irrigation systems, agricul-
tural projects or tree plantations.
Urban and periurban malaria are on the increase in south Asia and in
many areas of Africa. Military conflicts and civil unrest, along with
unfavourable ecological changes, have greatly contributed to malaria
epidemics, as large numbers of unprotected, non-immune and physi-
cally weakened refugees move into malarious areas. Such population
movements contribute to new malaria outbreaks and make epidemic-
prone situations more explosive.
The concentration of gold or gem mining and logging in the South
American or south-east Asian forested regions, where the continuous
flow of migrant workers are exposed to very high malaria transmis-
sion, also leads to epidemics. Moreover, these are the original foci of
multidrug resistance outside Africa, south of the Sahara.
Another disquieting factor is the re-emergence of malaria in areas
where it had been eradicated (e.g. Democratic Peoples Republic of
Korea, Republic of Korea and Tadjikistan), or its increase in coun-
tries where it was nearly eradicated (e.g. Azerbaijan, northern Iraq
and Turkey). The current malaria epidemics in the majority of these
countries are the result of a rapid deterioration of malaria prevention
and control operations, due to a variety of reasons.
The economic effects of malaria are especially noticeable in rural
areas, where malaria frequently strikes at the time of year when there
is greatest need for agricultural work. Furthermore, the disease is a
common cause of school absenteeism, reaching as high as 28% in
some places. The estimated annual direct and indirect cost of malaria
in Africa alone is more than US$ 2000 million.
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3. Implementation status of the Global Malaria
Control Strategy
The Committee reviewed the progress made since 1992 in the imple-
mentation of WHOs Global Malaria Control Strategy, the four basic
technical elements of which are:
to provide early diagnosis and prompt treatment of malaria;
to plan and implement selective and sustainable preventive mea-
sures, including vector control;
to detect early, contain or prevent epidemics;
to strengthen local capacities in basic and applied research to per-
mit and promote the regular assessment of a countrys malaria
situation, in particular the ecological, social and economic determi-
nants of the disease.
Additionally, an important consideration now is the prevention of the
re-emergence of malaria in countries that had either succeeded in
bringing down malaria incidence to a sporadic level, or had inter-
rupted transmission altogether.
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treatment of malaria persists and the continuing spread of parasite
multidrug resistance remains a matter for concern. There have been
many training programmes on clinical management of malaria but
more are needed, particularly within the private sector.
In the WHO European Region, disruption of the traditional links
between the newly independent states of the former Soviet Union has
resulted in difficult economic conditions. The exodus of trained staff
and a shortage of supplies have resulted in sudden and severe reduc-
tions in the quality of health care, including the diagnosis, manage-
ment and prevention of malaria. In several western European
countries, the fatality rate among imported falciparum malaria cases
(1.57.0%) is unacceptable and incompatible with the generally high
standards of medical care in the region suggesting that both diag-
nosis and management of the disease are inadequate.
In the WHO African Region, although coverage with treatment facili-
ties has improved overall, problems remain in many countries, espe-
cially those affected by civil disturbances. The introduction of cost
recovery for treatment in many countries has had variable conse-
quences. In some areas, the introduction of costs has had an adverse
effect on the management of malaria, especially when it has not been
accompanied by any improvement in the quality of care provided.
First- and second-line drugs of uncertain quality are in widespread use
in both the public and private sectors, and few countries in the region
have the resources to maintain surveillance of drug quality. The emer-
gence of P. falciparum resistant to chloroquine and sulfadoxine/
pyrimethamine in eastern and western Africa is a matter of concern
because of the much greater cost of alternative treatments.
In the WHO Region of the Americas, major advances have been
made in integrating traditional malaria control programmes into the
general health services. Although the efficiency of local health ser-
vices in the detection of malaria cases is considerably higher than
that of specialized services, it still requires strengthening in many
countries. The epidemiological redefinition of malaria risk areas has
resulted in the prioritization of areas and an improvement in the
targeting of diagnostic and treatment facilities to those in greatest
need.
The Committee gave particular attention to the review of three tech-
nical issues:
Management of severe malaria
Although the management of severe malaria in health facilities has
improved somewhat in many areas, problems remain, especially in
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Africa, south of the Sahara, where many patients with severe ma-
laria live in areas where there is no transport system available to
take them to hospital. In such circumstances, the provision of emer-
gency pre-referral therapy, such as rectally administered artemi-
sinins, may reduce mortality.
Antigen detection tests in diagnosis
Rapid tests for the diagnosis of malaria based on dipstick tech-
nology (see section 5.1.1) are being used frequently in western
Europe for visitors returning from malaria-endemic countries. In
India, they are being used selectively in both the public and private
sectors. Such tests are likely to prove of particular value in the early
detection of epidemics and of malaria in other emergency
situations.
Drug resistance
The expanding problem of drug resistance continues to challenge
malaria control efforts based on early diagnosis and treatment.
New antimalarial drugs and approaches to overcome parasite resist-
ance are needed to deal successfully with this challenge.
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include the difficulty of ensuring that nets are available to all who
need them, in particular the underprivileged. The fact that only one
class of insecticide (pyrethroids) can currently be used to treat nets
and that resistance to pyrethroids has already been recorded among
anopheline mosquitos is disturbing. In addition, the long-term effi-
cacy of this control measure has not yet been determined.
3.2.4 Chemoprophylaxis
In pregnancy
Few women resident in malaria-endemic areas currently receive ma-
laria chemoprophylaxis. In some countries, national guidelines rec-
ommend the provision of chemoprophylaxis during pregnancy but
little effort is made to implement this measure. In other countries,
chemoprophylaxis with chloroquine is available, but is only weakly
effective because of lack of patient compliance and P. falciparum
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drug resistance. There are at present no fully effective and feasible
approaches to prevent malaria in non-immune pregnant women in
endemic or epidemic-prone areas. It has been shown that infection
with P. vivax also adversely affects the outcome of pregnancy, and the
role of chemoprophylaxis and/or intermittent treatment in the man-
agement of this infection also needs to be examined.
In children
Chemoprophylaxis is generally not recommended for children who are
likely to have lifelong exposure to malaria.
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have been forced to take up appointments in areas that do not use
their expertise. It might be possible to recruit some of these scientists
back into malaria control, perhaps after some retraining, if their con-
ditions of service were improved.
3.5 Prevention of the re-emergence of malaria
The Committee noted that most of the countries that had achieved
malaria eradication were able to maintain this status. Additionally, a
number of countries have succeeded in eliminating P. falciparum,
while transmission of P. vivax still continues (e.g. Iraq, Morocco and
Syrian Arab Republic). In these countries, appropriate measures
should be planned to monitor the reintroduction of malaria and to
recognize episodes of renewed transmission, and to implement appro-
priate control measures.
In a number of countries, the incidence of malaria has been brought
down to such low levels that total interruption of transmission may be
a feasible objective (e.g. Algeria, Egypt, Morocco, Oman and United
Arab Emirates). For such countries, interventions could be planned
to achieve complete interruption of transmission based on the prin-
ciples of eradication.
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4.1 Decentralization of the health system
Decentralization, an essential strategy in the implementation of
health sector reform, involves the transfer of resources and authority
to district and sub-district levels. It should also empower local autho-
rities and communities to identify their priorities and needs. Health
issues should be addressed directly through enhanced community
awareness and knowledge about disease prevention, diagnosis and
treatment, as well as through local operational research activities.
The poorly managed decentralization of malaria control programmes
has undermined their effectiveness and hampered their ability to fulfil
their responsibilities. As a result of this decentralization, which often
occurs without any input from malaria control programme staff,
programmes that were previously highly effective have lost direction
and focus. In addition, experienced and dedicated personnel with
specific technical expertise have retired or moved to other positions.
Thus, programmes have lost the capability to respond rapidly and
effectively to changing conditions (e.g. epidemics), and their commit-
ment and ability to guide operations at the community level.
These losses have generally not been counterbalanced by the creation
and development of technical competence and resources at the dis-
trict and sub-district level, thus creating a vacuum in malaria control
expertise and implementation. As a result, many of the potentially
positive outcomes of decentralization, such as local ownership and
responsibility for the programme, more active community involve-
ment, increased ability to tailor control measures to local epidemio-
logical situations, and greater intersectoral collaboration, are not
being seen. Similar problems have also been observed in countries
which lacked an effective national control programme when the de-
centralization process began: such countries are left disorientated and
unable to deal effectively with the challenge of building up human
resources and technical competence at the central and local levels.
Effective management of malaria control activities requires that cer-
tain national-level competence and coordinating functions be retained
or developed at the central level of the programme (not necessarily the
nations capital) during the process of decentralization. These func-
tions include providing strategic direction to the programme, develop-
ing malaria policy at the national level, and setting standards, norms
and indicators for monitoring the progress of operational activities. In
addition, they include mobilizing and coordinating external funding,
epidemiological analysis, quality assurance, providing technical
training and support for malaria team members at the local level,
coordinating the response to epidemics, and evaluating and validating
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programme activities, including operational research undertaken at
the district level. Thus, effective management of control programmes
will require not only expertise in disease management, epidemiology,
surveillance and vector control, but also social, economic and behav-
ioural studies and adequate administrative, statistical and logistic
support. In countries where malaria is a high priority within the
ministry of health, part-time staff who do not work exclusively on
control programmes cannot normally provide this level of competence.
Important benefits of a decentralization policy to malaria control are
that decision-making and planning capacity would be based at the
level where the problems occur. At the district and sub-district levels,
where responsibility for the successful execution of control activities
is centred, functions required would include local-level planning,
resource allocation, disease surveillance, monitoring of programme
activities, health education, training and vector control. District staff
must serve as an effective liaison between field staff and national-level
staff and provide continuous operational guidance to the peripheral
level. Epidemiological information collected at the periphery should
be initially analysed at this level, with feedback and technical guid-
ance provided to field staff for rapid action, while the central team is
provided with a summary of the data on a regular basis for more
detailed analysis. Local capacity for surveillance and rapid response
needs to be strengthened, especially in high-risk and epidemic-prone
areas.
It is crucial that responsibility for the implementation of malaria
control activities at the district and sub-district levels be accompanied
by adequate funding. Furthermore, sufficient logistic support must be
provided to enable local authorities and staff to carry out their re-
sponsibilities and respond rapidly and effectively to changes in the
epidemiological situation.
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tality, any change which might influence the provision of prompt and
effective treatment is of critical importance to malaria control efforts.
Experience has shown that if the cost of treatment increases through
some form of user fees without any change in the quality of health
care, attendance at health facilities will fall and this will affect the
poor disproportionately. If, however, increased costs lead to improve-
ment in the quality of care, use of the facilities does not necessarily
decrease. An analysis of the impact of increased treatment costs on
the provision and quality of care in the Bamako Initiative, a large-
scale primary health-care project in Africa, south of the Sahara, in-
volving community health financing through a revolving fund for
drugs, showed mixed results. In some cases, the availability and de-
mand for drugs increased, while in others, it was possibly a disadvan-
tage for the poor.
Thus at present, there is no evidence that cost recovery per se has
resulted in improved quality of care. In fact, as costs are raised,
greater proportions of patients tend to seek antimalarial treatment
from private or informal sources, where they are typically treated
with inappropriate drugs or incorrect dosages. This may result in
increased morbidity and mortality. There is evidence from some
countries that user fees have also promoted irrational prescribing
practices in the treatment of malaria, such as subcurative treatments,
polypharmacy (i.e. prescribing multiple drugs), concomitant adminis-
tration of antibiotics and/or steroids, and the use of injections when
they are not indicated.
In spite of efforts to introduce health finance reforms for curative
services, most people would agree that preventive services should be
managed differently. Activities such as the Expanded Programme of
Immunization and provision of antenatal and postnatal preventive
services have been viewed as priorities for public financing. It has
always been accepted that indoor residual spraying should be publicly
financed, and it has also been suggested that chemoprophylaxis or
intermittent treatment for malaria in pregnancy should be provided
free of charge. The situation is, however, less clear with regard to
bednets and other insecticide-treated materials. It has been argued
that, given the disproportionate impact of falciparum malaria on
pregnant women and young children (under 5 years) in Africa, south
of the Sahara, these groups should be provided with free insecticide-
treated bednets as part of an antenatal or postnatal care package.
While this may seem attractive, experience has shown that this may
not be the best way to target these populations, as bednets often end
up being used by family members other than those for whom they
were intended, or sold to others. Therefore, it may be more effective
15
to provide insecticide-treated materials to everyone at a subsidized
price.
There is a need for national malaria control programmes to become
more proactive in defining their objectives for curative and preventive
care as health-care financing reforms take place. This will ensure that
the population groups most affected by malaria are not placed at a
disadvantage because they have to assume a disproportionately large
share of the cost of providing good-quality health services. Guaran-
teed access to early diagnosis and treatment of febrile illnesses is an
essential component of malaria control efforts. This could be accom-
plished if control programmes move towards the goal of providing
free diagnostic and treatment services to all.
4.3 Increased partnership with communities and the private
sector
The costs of extending public health services to the community level
have accelerated the process of involvement by communities and the
private sector as partners in malaria control. This can be expected to be
a slow but continuous process. So far, information is becoming avail-
able, largely from Africa, south of the Sahara, on the costeffectiveness
of three types of interventions undertaken at the community level: the
provision of widely available curative treatment, usually by village
volunteers; chemoprophylaxis for pregnant women; and the use of
insecticide-treated materials. Information is needed from different
epidemiological settings on the simultaneous use of such interventions.
While community-based interventions offer hope for the future, it is
difficult at present to draw conclusions about the types of interven-
tions that could successfully be delivered using community involve-
ment. In spite of evidence that early treatment of malaria in children
lowers case-fatality rates, it has been difficult to design community-
based distribution mechanisms that demonstrate an impact on mor-
tality. While it is clear that insecticide-treated materials for all and
chemoprophylaxis for pregnant women would save lives and are cost-
effective in research settings, it is not yet known whether they can be
delivered at low cost in a practical programme setting. Simultaneous
use of two or more of these interventions, which may be possible as
community involvement increases, offers promise of a synergistic
effect on severe morbidity and mortality.
5. Disease management
Disease management remains a fundamental and indispensable ele-
ment of malaria control. Its aims are to:
16
avoid the progression of mild malarial disease to severe or compli-
cated disease;
prevent death or sequelae from severe and complicated malaria;
limit the duration of disease;
prevent transmission of malaria in certain situations, especially
where transmission is low;
minimize the risk of selection and spread of drug-resistant
parasites.
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5.1.1 Diagnosis
The diagnosis of malaria can be based on clinical criteria and/or
techniques for parasite detection.
Clinical diagnosis
As most cases of malaria are still treated on the basis of clinical
diagnosis, it is inevitable that many patients without the disease re-
ceive antimalarial drugs. This causes unwarranted costs for patients
and/or health services, risks of side-effects, and if the drugs are long-
acting, this may lead to the selection of resistant parasite strains.
Conversely, lack of sensitivity of clinical criteria may cause some
patients suffering from malaria not to be treated, thereby risking
progression to severe disease and death.
While it is important to establish clinical diagnostic criteria which
minimize the number of patients who receive the wrong treatment,
improving diagnostic sensitivity has high priority given the high
case-fatality rate of untreated falciparum malaria. A full assessment
of the patient is always needed, since simply equating fever with
malaria may lead to other curable conditions being overlooked.
Unfortunately, the signs and symptoms of malaria, such as fever,
chills, headache and anorexia, are generally nonspecific. Recent
studies have identified some signs and symptoms which, especially
in combination, have diagnostic value in specific epidemiological and
operational situations (57). However, it is not possible to apply any
one set of clinical criteria to the diagnosis of all types of malaria in all
patient populations. Experience has shown that clinical diagnostic
criteria must vary from area to area according to the intensity of
transmission, the prevalent species of malaria parasite, the incidence
of other causes of fever (e.g. dengue), the qualifications of health-care
providers, and health-service infrastructure.
In general, in settings where the risk of malaria is low (i.e. in areas of
low endemicity or, where malaria is highly seasonal, during the low-
transmission season), clinical diagnosis of uncomplicated malaria is
based on the degree of exposure to malaria, and a history of fever1
with no features of other severe diseases. The absence of an alterna-
tive explanation for the fever has been recommended but, according
to most studies, this will exclude only a small proportion of patients
with fever from unnecessary treatment (8). The Integrated Manage-
ment of Childhood Illness materials (2) provides clinical criteria,
1
In this context, history of fever means the presence of fever and/or a history of fever
within the past 4 days.
18
based on data from Africa, for treatment of children in low-risk settings.
These are fever, without a runny nose or measles, and no other appar-
ent cause of the fever. However, there is a need for more local clinical
epidemiological research on specific criteria for the diagnosis of falci-
parum malaria in both children and adults, and for vivax malaria.
In settings where the risk of malaria is high (i.e. in areas where
malaria transmission is stable or during the high-transmission season
of seasonal malaria), the accepted criteria for the treatment of ma-
larial disease in young children (generally below 5 years, but this
depends on the level of endemicity) and pregnant women are a his-
tory of fever or the presence of clinically detectable anaemia, for
which pallor of the palms seems to be the most reliable sign in young
children (9). In older children, adult males and non-pregnant women,
the sole criterion is a history of fever. The incidence of malarial
disease in these age groups is generally low, and therefore the absence
of an alternative explanation for the fever may be useful, especially in
drawing attention to other conditions that may need to be treated.
In malaria epidemics, all patients with a history of fever should nor-
mally be treated for the disease.
1
Parasite detection is used here as a common term for microscopical examination of
blood for Plasmodium species and immunological techniques for detection of plasmo-
dial antigens in blood.
19
of patients are very high, it may be warranted to restrict microscopical
analysis to severely affected patients and suspected treatment failures.
The detection of malaria parasites using the quantified buffy coat
(QBC) technique is easy to learn, has high sensitivity and specificity
and is quicker to perform than standard microscopy. However, this
technique requires specialized equipment and consumables, making it
prohibitively expensive. It is therefore unlikely to be used by health
services in the majority of endemic countries.
Among the available antigen-based tests (dipsticks), those based
on P. falciparum histidine-rich protein II (HRPII) detection have
been most extensively investigated under field conditions. Such tests
have good sensitivity for asexual P. falciparum, with a detection limit
of 60 asexual parasites per microlitre (10), although expert micros-
copy can detect as few as 4 asexual parasites per microlitre. However,
the quality of microscopy is sometimes so poor that microscopy can-
not be used as a basis for diagnosis. In such circumstances, antigen
detection tests are often at least as sensitive and specific as routine
microscopy at the periphery of the health services.
The acceptance of antigen test results as a basis for decisions on
whether to give treatment depends on the parasite density threshold
for disease in the patient population. One problem with HRPII-based
tests is the persistence after effective treatment of HRPII antigenae-
mia (11), possibly making these tests less suitable for identifying
treatment failures. Newer tests based on the detection of parasite-
specific lactate dehydrogenase have the advantage that they can detect
other species than P. falciparum, and they are not persistently positive
after effective treatment (12). Although they have not yet been as
extensively field-tested as the HRPII-based tests, they are commer-
cially available.
Dipstick tests are already in use in certain countries (e.g. Brazil,
Cambodia and India). These tests can be learnt within a few days and
are easy for clinical and paraclinical staff to use in peripheral health
facilities. The main obstacle to their widespread use in health care in
malaria-endemic areas is their cost, which is still more than US$ 1 per
test. As the price of first-line treatment goes up, and it is hoped
the price of dipstick tests goes down, it is likely that these tests will
become widely available as an effective and appropriate tool for
improved targeting of antimalarial drugs to the patients who need them.
Research on operational issues associated with antigen detection tests
and microscopy, including costeffectiveness and willingness to pay, is
of great importance in areas where there is need for improvement of
the current practice of clinical diagnosis.
20
Treatment of uncomplicated malaria
The principles of treatment of malaria are well described (4, 13, 14).
In many parts of the world, the selection of first-line treatment for
uncomplicated malaria is extremely difficult because of increasing
drug resistance of P. falciparum and, more recently in some areas, of
P. vivax. The factors to be taken into account (15) are:
drug effectiveness (which is determined mainly by efficacy (see
below), patient compliance and drug quality);
drug side-effects, tolerance, costs, affordability, availability and
acceptability to the consumer and provider;
characteristics of the health services.
In the decision-making process, it is essential to define efficacy by
clarifying the objective of treatment. There are basically two situa-
tions in which the objectives will differ:
Where malaria transmission is intense, most patients are semi-
immune and asymptomatic infections are common. The objective of
treatment is to obtain a clinical cure (i.e. clearance of signs and
symptoms, but not necessarily of parasites). Antimalarial treatment
must be schizonticidal but not necessarily gametocytocidal.
Where transmission is unstable, there is no significant immunity and
asymptomatic infections are rare. The objective of treatment is
to obtain a radical cure, since clinical cure can rarely be achieved
without parasite clearance. In certain circumstances, it may be nec-
essary to reduce the reservoir of infection by supplementing schi-
zonticidal treatment of falciparum malaria with a gametocytocidal
drug, usually primaquine in a single dose (4). The public health
benefits must be weighed against the small risk of side-effects and
the costeffectiveness of such a measure.
At present, chloroquine is still the preferred first-line treatment for
malaria caused by any Plasmodium species sensitive to the drug.
When a patient population with falciparum malaria does not respond
satisfactorily to chloroquine, the treatment of choice is sulfadoxine/
pyrimethamine or amodiaquine, although it must be remembered
that cross-resistance between chloroquine and amodiaquine has been
reported (16). (Criteria for a satisfactory response are described in
section 6.)
Ideally, the first dose of the drug should be given under observation.
In the case of a single-dose treatment, such as sulfadoxine/
pyrimethamine, this will ensure adequate treatment. With a multiple-
dose regimen, it will provide an opportunity to educate the carer and
patient about correct treatment.
21
When the response to sulfadoxine/pyrimethamine and amodiaquine
is no longer satisfactory, the choice of treatment becomes difficult.
Despite its price and side-effects, mefloquine would be the most
appropriate choice because of the simplicity of administration in one
or two doses. However, use of mefloquine as first-line treatment in
areas with intense transmission (e.g. Africa, south of the Sahara) is a
cause for serious concern, because the long half-life of the drug may
expose reinfecting parasites to subcurative drug concentrations that
could select for mefloquine-resistant strains (which are often cross-
resistant to quinine (17)). The alternative to mefloquine is quinine,
given three times a day for 57 days. To ensure a high cure rate,
quinine is normally given in combination with another drug, usually
doxycycline or tetracycline. Apart from the fact that doxycycline and
tetracycline cannot be given to children under 8 years or to pregnant
women, this regimen has the further disadvantage that patient
compliance is very low because of the need to take quinine, which
has important side-effects, three times a day. Clindamycin, an alterna-
tive to doxycycline that could be used for children and pregnant
women, is currently far too expensive to be of use in general health
services.
Among the affordable options in malaria-endemic countries, interest
is now focusing on artemisinin drugs because of the results of their
use over the last 20 years, especially in China, Thailand and Viet Nam
(18). These drugs are rapid acting, effective against all strains of P.
falciparum and P. vivax (particularly for the treatment of severe
malaria) and are well tolerated.
Owing to the limited amount of research carried out on the
artemisinins and concern that their unregulated use could lead to
parasite resistance, WHO has until recently recommended that
artemisinins should be used only in areas with multidrug-resistant
falciparum malaria (4, 15). In reality, however, as a result of market
pressure they are already widely available, especially in the private
sector, in most malaria-endemic countries. In this situation, their
uncontrolled use could lead to the appearance of parasite-resistant
strains without bringing much benefit to the most vulnerable
populations.
So far, resistance to artimisinin drugs has not been documented,
although relatively low in vitro parasite susceptibility has been ob-
served in southern China (W.H. Wernsdorfer, personal communica-
tion, 1998). Despite neurotoxicity in animal studies at doses that far
exceed those used for the treatment of malaria in humans, serious
side-effects in humans have not been encountered. The disadvantage
22
of these drugs, which is probably related to their short half-life, is that
they must be given for at least 5 days for acceptable cure rates to be
achieved. For this reason, which is a serious hindrance to compliance,
and to reduce the risk of resistance, artemisinins should always be
given in combination when used as part of malaria control in endemic
countries. Numerous trials have shown that cure rates close or equal
to 100% can be attained by giving the well tolerated combination of
an artemisinin drug with mefloquine for 3 days (18). Combinations
with other drugs also seem to be effective, but have not yet been
studied so widely.
Trials are now taking place to investigate the efficacy and safety of a
combination of artesunate and sulfadoxine/pyrimethamine. A fixed
combination of artemether with lumefantrine has already been regis-
tered, although the company has yet to develop a pricing strategy.
Alternative options for combination with artemisinin derivatives
include pyronaridine, chlorproguanil/dapsone and atovaquone/
proguanil, although atovaquone/proguanil is still too expensive for
endemic countries. If an artemisinin drug with sulfadoxine/
pyrimethamine combination proves safe and effective, it can be
recommended as routine first-line treatment in most countries where
chloroquine resistance is a problem. Given that sulfadoxine/
pyrimethamine resistance already exists, the useful life of this com-
bination would perhaps be limited, and research on the alternatives
mentioned above has high priority. If one of these combinations
proves safe and effective, it should be introduced as a replacement for
artesunate plus sulfadoxine/pyrimethamine. The replacement would
probably have a longer useful life, because there is as yet very little
reported resistance to the components. In addition, pyronaridine
as well as chlorproguanil/dapsone are better matched kinetically to
artesunate than is sulfadoxine/pyrimethamine.
The precondition for such combinations being effective is their cor-
rect use. Their large-scale distribution in package form, for example,
a blister-pack where the two components are kept together, would
improve compliance. A fixed combination formulation would be even
better, but this will still take years to develop. The use of artemisinin
drug combinations must be undertaken in a responsible way by public
health services that can ensure that health staff are trained in their
use. In addition, the drugs should not be available without the re-
quired information supplied in a locally appropriate form. Correct
drug treatment requires diagnosis to be more specific than is currently
the case in most places, and the drugs should be free or affordable to
the patient populations, so that poverty does not become a cause of
underdosing. Finally, the introduction of such combinations should be
23
accompanied by monitoring of their impact on mortality and inci-
dence of severe disease (see section 9).
Chloroquine-resistant P. vivax is so far not a public health problem
because it occurs mainly in areas with intense transmission where
most patients are semi-immune, so that chloroquine still has accept-
able effectiveness. P. vivax cases that fail to respond to chloroquine
may be treated with, for example, quinine or mefloquine. In some
settings, especially where transmission is not very intense, treatment
with primaquine is routinely indicated on clinical grounds to prevent
relapse of P. vivax infections (4, 14).
24
(19), there is currently great interest in developing training, specifi-
cally for the people who sell drugs to patients and their carers. This
may prove an efficient way of improving patterns of drug use, espe-
cially if combined with health education for mothers, other carers and
patients. However, there is still a need for field research to examine
whether activities directed at drug sellers can, in the long term, lead to
more rational use of drugs.
In all circumstances, appropriate training and/or information must be
given at the level where drugs are sold and used. Ideally, first-line
drugs, and information about them, should be available through the
private sector.
With drug policies changing and new treatments becoming available,
there is great concern that the drugs available at the periphery are of
good quality. Substandard drugs have an impact on the effectiveness
and safety of treatment, and parasite drug resistance. It is therefore
essential, especially with the introduction of artemisinin derivatives,
to strengthen national capabilities for quality control, and over time,
also for quality assurance.
25
inability to drink
persistent vomiting.
For adults, the same signs and symptoms are valid, with the addition of:
dark and/or limited production of urine.
Patients with prostration and/or breathing difficulties should, if at all
possible, be treated with parenteral1 antimalarials and antibiotics. If
the clinical condition permits, other patients may be treated with oral
antimalarials that must be fully effective.
For settings where patients with severe malaria present regularly and
it is not possible to refer them rapidly to facilities able to treat severe
malaria, a basic package for initial treatment could be made available,
supported by training and supervision. There are initial encouraging
results from Malawi on the provision of such a package. The training
should emphasize that, if at all possible, patients who have improved
after initial treatment, but are still ill, should be referred.
The contents of the package may vary according to the location, but
the minimum should include:
a parenteral antimalarial
a parenteral antibiotic
an effective oral antimalarial
a rectal anticonvulsant.
The parenteral antimalarial drug should be quinine, an artemisinin
derivative or sulfadoxine/pyrimethamine, if the parasite is known to
be susceptible to the latter combination.
Rectal formulations of artesunate are now more available and are
likely to be chosen for pre-referral treatment of severe malaria. How-
ever, attention should be paid to the need for a complete curative
treatment.
It may be necessary, especially if quinine is used, to provide glucose
intravenously or via a nasogastric tube. However, there are serious
doubts about whether liquids can be given safely by either of these
routes outside hospital. This issue should be examined by operational
research under local conditions.
A rectal anticonvulsant, for example, diazepam, is to be used in the
case of convulsions. Recent research indicates that routine adminis-
tration of phenobarbital may increase mortality in children with se-
vere malaria (K. Marsh, personal communication, 1998).
1
Normally, parenteral administration will be intramuscular.
26
6. Drug resistance of malaria parasites
6.1 Monitoring of drug resistance
The primary objective of monitoring drug resistance is to evaluate the
efficacy of the recommended treatment options for malaria at the
local level, with particular emphasis on falciparum malaria. The most
suitable method to achieve this objective is monitoring the therapeu-
tic efficacy of antimalarial drugs (21), which has been recently modi-
fied1 by WHO to replace the standard in vivo test. Other levels of
monitoring exist, including in vitro susceptibility testing of parasites
and the study of genetic markers of resistance, both of which are very
useful for specific research purposes (see sections 6.1.2 and 6.1.3).
1
Assessment of therapeutic efficacy of antimalarial drugs for uncomplicated falciparum
malaria. Geneva, World Health Organization, 1997 (draft document 29.2.97; available on
request from the Roll Back Malaria project, Communicable Diseases, World Health
Organization, 1211 Geneva 27, Switzerland).
27
whenever there are increasing numbers of clinical reports of drug
failures. The proportion of early and late treatment failures after
supervised treatment should help policy-makers decide whether to
update the malaria treatment guidelines.
Monitoring of therapeutic efficacy is complex and requires specific
technical expertise. Given the present requirements of the test, gen-
eral health service staff with minimal supervision are unable to carry
it out. However, the protocol can be used to train staff of the national
malaria control programmes in operational research methods. The
core protocol can be used in field trials of antimalarial drugs or drug
combinations, and whenever possible, the basic observations should
be incorporated into new clinical trials, so that the results can be used
to monitor therapeutic efficacy.
The most important requirements for effective monitoring of thera-
peutic efficacy are the selection of a minimum number of representa-
tive sites, and maintenance of quality in the performance of the study.
The evidence available does not allow simplification of the method,
and further research on early predictors of treatment failure is needed
to develop a test of shorter duration. The current test, however, can
provide the basis for further research and investigators can add other
observations (e.g. day 5, day 11 or day 28 follow-up examinations) to
the basic test to address specific issues. The long-term goal, however,
remains to develop procedures which can be incorporated into rou-
tine patient management, permitting continuous monitoring of drug
response.
Interpretation of the clinical response will be determined mainly by
the objective of malaria treatment (i.e. clinical or radical cure), in-
stead of endemicity levels (15). In Africa, where clinical cure is the
objective of treatment, a follow-up of 14 days has been adopted for all
age groups in areas of low or moderate transmission, and only for
children under 5 years in areas of intense transmission. In countries
where treatment aims at radical cure, a minimal duration of 14 days is
recommended for the test, if follow-up at 21 and 28 days is not
feasible.
Although P. vivax resistance to chloroquine has been reported in a
few countries, this has so far had a limited effect on the clinical
management of patients with vivax malaria. The therapeutic efficacy
of chloroquine against P. vivax could be monitored using a protocol
developed for P. falciparum.
With more experience and research, the methodology for monitoring
drug resistance should be refined on a regular basis. Of specific inter-
28
est will be research to determine the significance of early and late
treatment failures, in terms of the risk of rapid progression of the
disease to severe malaria and death; persistent morbidity; and the
burden on the health facilities resulting from recurrent unsuccessful
treatment.
29
6.2 International monitoring of the drug response of
P. falciparum
The main objectives of international monitoring of drug resistance
are to analyse the dynamics of drug resistance and share the informa-
tion among countries. As part of the analysis, the international moni-
toring may also serve to check and evaluate drug utilization strategies
or other malaria control activities aimed at reducing or preventing the
selection of parasite resistance.
A limited number of centres need to be established in Africa, south of
the Sahara, and elsewhere as repositories of parasite isolates (from
blood samples, fingerpricks taken at the time of clinical failure and
blood smears) for studies on drug resistance, malaria genetics, immu-
nology and pharmacology.
The capability for pharmacokinetic studies should be strengthened at
the regional level. Selected WHO Collaborating Centres should be
used for such studies and for training purposes.
30
resistant to the first-line treatment, effective second-line treatment
must always be available.
The development of appropriate legislation is important to improve
drug registration and the use of drugs (especially in the informal
sector). Such legislation will also help establish effective mechanisms
for drug quality control. WHO should strengthen capacity for quality
control of antimalarial drugs on a regional basis.
31
in areas with P. falciparum multidrug resistance, after prior screening
for glucose-6-phosphate dehydrogenase deficiency (25).
32
malaria endemicity often show this periodicity and can also be con-
sidered as epidemic prone, whether they are the fringes of deserts or
the upper limits of highlands.
Epidemic-prone areas can be classified, according to the main factors
responsible for triggering an epidemic, into:
Endemic areas subject to a sudden increase in the number of
exposed non-immune individuals, caused by:
the arrival en bloc of non-immune populations (e.g. refugees or
displaced populations) into a malarious area;
the mixture of large numbers of immune and non-immune
people living in primitive conditions (e.g. in temporary labour
camps and development project sites).
Hypo- or meso-endemic areas subject to a sudden increase in vec-
torial capacity, caused by:
an abrupt rise in Anopheles density due to abnormally heavy
rains, and/or increased survival of the mosquitos due to pro-
longed warm and humid weather;
acceleration of the parasite sporogonic cycle due to ex-
ceptionally long and warm summers;
invasion of a more efficient vector into areas where local vectors
were not able to maintain intense transmission, or areas where
no vector previously existed.
Hypo- or meso-endemic areas subject to environmental mod-
ifications which may lead to both increased vector density and
human population movement, such as:
agricultural development;
rapid, uncontrolled growth of cities in tropical areas.
Previously endemic areas, which fail to maintain previously effec-
tive controls because of:
resurgence of malaria transmission (leading to post-eradication
epidemics);
progressive spread of parasite chloroquine resistance, par-
ticularly in Africa, south of the Sahara, during the past two
decades. While in some situations, parasite drug resistance has
assumed epidemic proportions, epidemics often act as a major
vehicle for the spread of drug-resistant strains.
33
epidemic-prone areas, this preparedness should come from an appro-
priate prediction system based on monitoring epidemic risk factors.
Epidemic and emergency preparedness is being promoted as an es-
sential activity of health services. In line with this, WHO is supporting
the organization and work of intercountry emergency preparedness
teams in Africa which will collaborate with affected countries. In
epidemic-prone areas, it is essential that a close collaboration is estab-
lished between the specialized antimalarial services and the emer-
gency preparedness teams. The specialized services could then assist
in the:
identification of epidemic-prone areas, the main risk factors and
alarm signals;
monitoring of risk factors;
planning, implementation and evaluation of preventive or control
measures, taking into account essential epidemiological character-
istics (e.g. parasite sensitivity to drugs and vector susceptibility to
insecticides).
The concept of risk detection should be considered in relation to the
time available for implementing an appropriate response. After rec-
ognizing an imminent epidemic risk, it is particularly important to be
able to estimate the potential magnitude of the forthcoming epidemic
wave, as well as the area of potential spread.
34
As most malaria epidemics are the result of abnormal meteorological
conditions, climate monitoring will provide the most useful indicator
of epidemic risk. Analysis of past records will permit the identification
of alarm signals (e.g. early and prolonged rains, floods and monsoon
failures), which could alert the epidemic preparedness system to pre-
pare an adequate response.
Information from meteorological satellites, particularly the normal-
ized difference vegetation index (NDVI),1 may be very useful in the
identification, confirmation and demarcation of epidemic-prone
areas. The usefulness of satellite data as risk indicators is limited, as
rain monitoring provides an earlier warning. Consideration should
nevertheless be given to the potential usefulness of other indicators
obtained by satellite, such as cold cloud duration (CCD),2 if they can
be obtained earlier than currently possible.
Monitoring the relevant meteorological variables remains the most
useful indicator in areas where the risk of epidemics is associated
with:
drought, such as the failure of the south-west monsoon in the
malarious intermediate zones of Sri Lanka;
abnormally high temperature, such as in the highlands (around
2000 m) of east Africa.
Epidemics resulting from environmental modifications or social dis-
turbances will require the continued alertness of malaria epidemiolo-
gists to the social and economic conditions in malarious or potentially
malarious areas.
Early detection of epidemic situations requires a definition of normal-
ity. The most practical method is the determination of epidemic indi-
ces by plotting the median and the third quartile of the malaria
incidence (or merely the numbers of malaria cases) every calendar
month of previous years. This defines a normal range on which to plot
the current data in order to detect an abnormal increase. Malaria
programmes should support district medical officers to ensure that at
least a few health facilities (hospitals and health centres) in epidemic-
prone areas adopt this method of epidemiological analysis.
1
Used as a proxy for monitoring growth and types of and changes in seasonal vegetation.
2
Used as a proxy estimate for rainfall.
35
followed by the implementation of measures, which may consist of
the following:
transmission prevention measures (e.g. indoor residual spraying)
before the start of the epidemic, if resources are available;
if such measures cannot be implemented in time, it is necessary to
ensure that there are adequate stocks of antimalarial drugs, sev-
eral fold above normal levels of consumption, and strengthen the
systems for early detection of emerging epidemics, in as many as
possible of the health-care facilities in the area at risk.
The response to a reported epidemic, from whatever source (health
services, private health providers, political authorities or the press)
should include:
1. Confirmation of diagnosis (parasite species, if possible); recording
the severity, duration of illness, occurrence of deaths, and consis-
tency of case definitions. If malaria is confirmed, the parasite
species involved and transmission dynamics should be documented.
2. Demarcation of the affected area.
3. Assessment of the local capacity (health services, community par-
ticipation and intersectoral collaboration) to manage the situation
and of the need for assistance from within the country and perhaps
from international collaborators.
4. Strengthening diagnostic and treatment facilities within the health
services and in whatever informal systems can be mobilized (e.g.
local authorities and organizations, schoolteachers and home drug
suppliers).
5. Planning and organizing emergency control measures, possibly
implementing selected interventions in time to influence the
course of the epidemic.
It should be emphasized that, ideally, the work described in points
35 should be carried out well before the outbreak of an epidemic.
The main objectives of epidemic control should be to:
provide adequate relief to the affected population;
contain transmission, if possible, in the affected areas;
prevent further spread of the epidemic;
improve emergency preparedness in order to prevent future
epidemics.
Emergency control may include mass drug administration or, prefer-
ably, mass treatment of fever, which normally includes treatment of
every patient complaining of current or recent fever, and everyone in
the patients household. These measures are mostly indicated in the
36
case of refugees or displaced populations before a health-care system
can be organized in the camps. The drug selected for mass treatment
should have recognized effectiveness, but its use should not threaten
the supplies needed for the treatment of actual cases. The objective of
mass drug administration is to reduce rapidly the parasite reservoir
during the period of intense transmission. Primaquine, if available,
should be added to the drug regimen for its gametocytocidal effect.
All efforts should be made to control transmission (e.g. by space
spraying and indoor residual spraying) whenever mass drug adminis-
tration is implemented, as mass treatment of a non-immune popula-
tion at a time of very intense transmission will exert a high selection
pressure for parasite drug resistance.
8. Prevention of malaria
The Global Malaria Control Strategy stresses the selective use of
preventive measures wherever they can lead to sustainable results.
Such measures should be aimed at halting the deterioration of the
malaria situation, minimizing the wasteful use of resources and con-
tributing appropriately to the development of health services,
intersectoral cooperation and community participation.
37
humanvector contact cost-effectively, while addressing sustainability
issues. Implementation of control measures depends on a number of
factors, such as malaria epidemiology, the available information, the
potential and limitations of each method, infrastructure and institu-
tional capacities. These vary within and among countries and regions.
38
countries, DDT has been banned for use in agriculture and a number
of countries have extended this ban to public health applications.
Several other countries (e.g. India, Mexico and South Africa) are
considering or have decided to phase out DDT use in their public
health services over periods of between 3 and 8 years.
In accordance with their mandate, previous meetings of the relevant
WHO Expert Committees and Study Groups have focused mainly on
the human toxicological aspects of DDT and other insecticides. The
targeted application of insecticides to indoor walls in order to inter-
rupt disease transmission greatly reduces dispersion of the chemicals
into the environment. For this reason, the environmental risks from
such targeted measures were considered minimal, certainly when
compared to those associated with agricultural applications, in which
the quantities of insecticides released are much greater than for public
health use. Environmental protection agencies argue, however, that
significant amounts of DDT intended for public health use still end up
in the agriculture sector through illicit trading practices, and therefore
in the environment. There are insufficient data available for exact
quantification, but the significance of this is thought to be minimal. It
is clear, however, that in the broader context of sustainable develop-
ment and in line with the principles agreed at the United Nations
Conference on Environment and Development (27), WHOs concern
now goes beyond human toxicology to the impact of DDT use on the
earths resources and biodiversity.
39
long term. Therefore donors should be encouraged to contribute to
more sustainable programmes.
To improve the affordability of mosquito nets and insecticides, appro-
priate measures (e.g. tax exemption, price control and exceptional
inclusion of both the nets and insecticides in a list of essential drugs)
need to be considered. Social marketing is regarded as an important
initiative to create demand that will progressively be supplied by the
commercial sector. However, the public sector should ensure quality
assurance for netting materials and insecticides. Simple tests for
monitoring the presence of insecticides on nets need to be developed
as a matter of urgency.
Re-treatment is a critical component of sustainable programmes for
promoting the use of insecticide-treated materials. Therefore, promo-
tional activities to increase peoples awareness of the need to re-treat
materials should be intensified. Several options for re-treatment are
available, including providing individual doses (in the form of sachets
or tablets), which are thought to make insecticides more affordable at
the peripheral level. However, careful monitoring of re-treatment of
materials is important for detecting both inadequate and excessive
doses of insecticides. Methods to improve the wash-resistance of in-
secticide deposit, such as by permanent impregnation, also need to be
further investigated.
The impact of insecticide-treated nets on overall mortality has been
clearly established. However, there is a need to monitor their long-
term effect on the immunity of the human population and the resist-
ance and behaviour of the mosquito population. Admission of
patients to hospital with anaemia or severe malaria may serve as a
rough indicator of trends in morbidity and mortality related to ma-
laria control activities, including the use of impregnated materials.
Monitoring and evaluation of the use of insecticide-treated materials
should be integrated into all malaria control programmes.
40
malaria, not only in the immediate vicinity of the project or on those
involved in it, but also in the whole area influenced by the project.
If such assessment is properly conducted at the planning stage, a
relatively minor investment, properly guided, will not only result in
the prevention of man-made malaria, but could also contribute to
better control of malaria in all the areas influenced by the project. In
contrast, failure to conduct an assessment at the planning stage will
frequently result in malaria epidemics or resurgence of the disease
with high morbidity and mortality, and will require major investments
to control the situation.
These principles are now widely accepted, but are not always put into
practice during the planning phase for financial or other reasons.
Management of malaria during development projects requires
intersectoral collaboration, and provides an opportunity to establish
links between workers in different disciplines that could be of value in
other malaria control programmes not related to the development
project.
Current examples of environmental management of malaria through
vector control also need to be documented.
41
In epidemic-prone areas and areas with a very short malaria transmis-
sion season, indoor spraying is more suitable than using impregnated
materials to contain epidemics.
8.2 Chemoprophylaxis
The available drugs for chemoprophylaxis are limited to chloroquine,
proguanil, pyrimethamine/dapsone, mefloquine and doxycycline. In-
creasing parasite drug resistance and drug-specific side-effects make
rational guidelines for chemoprophylaxis more and more difficult to
compile. There is no ideal drug for prophylaxis. Chemoprophylaxis is
limited to travellers, special groups (e.g. armies) and, in certain situa-
tions, pregnant women.
42
avoidable and unacceptably high maternal and infant mortality.
Health care for these women must be a comprehensive package,
based on the extent of the problem and opportunities for inter-
vention. In areas of high malaria transmission, this package should
include prevention of malaria infection through health promotion and
intervention, as well as methods to reduce the consequences of infec-
tion. This will include the use of antimalarials as prophylaxis or as
intermittent treatment, possibly the use of insecticide-treated mos-
quito nets, and access to early diagnosis and effective treatment for
anaemia and clinical malaria.
In endemic areas, effective prevention of malaria in pregnancy
decreases the incidence of low birth weight and severe maternal
anaemia. Weekly chemoprophylaxis used to be the method of choice,
but chemoprophylaxis is increasingly hampered by parasite drug
resistance, contraindications of certain drugs and poor patient com-
pliance. In the search for alternative strategies, intermittent
therapy has been proposed as a simple and cost-effective method in
highly malarious areas. Intermittent therapy involves the administra-
tion of full, curative-treatment doses of an effective antimalarial drug
at predefined intervals during pregnancy.
In areas of east Africa with increasing chloroquine resistance, large-
scale trials have shown that intermittent treatment with a single-
treatment dose of sulfadoxine/pyrimethamine at the beginning of the
second and third trimesters significantly reduces the prevalence of
anaemia and low birth weight the latter being the greatest single
risk factor for infant mortality. Studies in Kenya and Malawi indicate
that rates of placental malaria, severe anaemia and low birth weight
can be significantly reduced if women in their first and second preg-
nancies receive intermittent sulfadoxine/pyrimethamine as part of
antenatal care. Furthermore, the drug was well tolerated by pregnant
women, and adverse reactions were uncommon (3033, A. Machesa,
personal communication, 1997).
In Malawi, intermittent sulfadoxine/pyrimethamine was successfully
introduced in 1993 as national policy for the prevention of malaria
in pregnancy, resulting in a decrease in the incidence of low birth
weight in women in their first pregnancy (34). It can be concluded
that in areas where there is a high risk of P. falciparum infection in
pregnancy, where P. falciparum is susceptible to sulfadoxine/pyri-
methamine and where the treatment regimen can be administered
correctly, intermittent treatment with sulfadoxine/pyrimethamine is
safe and effective for reducing the consequences of malaria in preg-
nancy. In malaria-endemic areas, comparing the birth weights of
43
first-born infants with those of infants born to mothers who have had
several pregnancies may be a suitable indicator of the efficacy of
malaria control in pregnancy. This ratio of birth weights may be used
to identify the endemic areas where malaria control in pregnancy is
inadequate and where intermittent treatment is beneficial to pregnant
women (35).
Further studies in Kenya and Malawi demonstrate reduced efficacy of
intermittent sulfadoxine/pyrimethamine treatment in HIV-infected
pregnant women, indicating that these women may require more
frequent intermittent treatments (30, 36). There are indications that
HIV infection may interfere with the maintenance of pregnancy-
specific immunity acquired during first and second pregnancies, plac-
ing HIV-infected women who have had several pregnancies at risk of
the severe consequences of malaria in pregnancy (37).
44
use of pyrethroids in agriculture and household pest control. The gene
can be maintained at a low frequency in mosquito populations over
decades. Pyrethroid resistance has already been found in some
important malaria vectors such as An. gambiae s.s. in west Africa,
An. albimanus in Central America, An. sacharovi in Turkey and
An. stephensi in India, Pakistan and parts of the Arabian Peninsula.
The impact of kdr on the behaviour of An. gambiae s.s. and the
efficacy of pyrethroid-treated nets has been recently investigated
using experimental huts in two countries of west Africa (Benin and
Cte dIvoire). For each country, a comparison was made between
areas where mosquitos were resistant and where they were suscep-
tible. Although the allelic frequency of kdr was very high (more than
80%) in areas of resistance in both countries, permethrin- and
deltamethrin-treated nets still offered protection against mosquitos:
the repellent and killing effects, as well as reductions in blood feeding,
were maintained at similar levels in both resistant and susceptible
areas. The impact of kdr is to be further evaluated at the operational
level when nets are used for community protection mass killing of
the mosquito population is expected. It will be also important to
assess the impact of pyrethroid resistance mechanisms other than kdr,
such as esterases or oxidases. So far, kdr has only been found in the
savanna form of An. gambiae s.s. and in west Africa, but its presence
has also been strongly suspected in An. stephensi, An. albimanus and
An. sacharovi.
In areas where kdr is currently absent, it is unlikely to be selected by
the use of insecticide-treated materials alone. However, other mecha-
nisms may also be involved in pyrethroid resistance, some of which
are already found in malaria vectors. Considering the increasing use
of pyrethroids in agriculture and in urban areas, the development of
pyrethroid resistance in malaria vectors should be regarded as a very
important issue.
Networks for monitoring insecticide resistance in malaria vectors
have been recently launched in Africa. In addition to classical bio-
assays, the resistance mechanisms involved will be identified and their
impact on the efficacy of impregnated materials evaluated. Similar
networks should also be established in other areas where vector con-
trol is envisaged.
Although considerable hope is now centred on the use of insecticide-
treated materials, its success relies almost entirely on pyrethroids,
which are the only insecticides currently available for this purpose.
Therefore, a high priority must be given to the search for non-
pyrethroid insecticides for treating materials. The search for effective
45
and practical strategies for management of insecticide resistance in
mosquitos should be encouraged. Every effort should be made to
prolong the useful life of available insecticides and to develop alterna-
tive preventive measures.
46
In areas without access to laboratory-based diagnosis:
Case of probable uncomplicated malaria a patient with signs and/
or symptoms of uncomplicated malaria, who receives antimalarial
treatment.
Case of probable severe malaria a patient requiring hospitaliza-
tion for signs and/or symptoms of severe malaria, who receives
antimalarial treatment.
Probable malaria death death of a patient who has been diag-
nosed with probable severe malaria.
In areas with access to laboratory-based diagnosis:
Asymptomatic malaria laboratory confirmation (by microscopy
or immunodiagnostic test) of parasitaemia in a person with no
recent history of signs and/or symptoms of malaria.
Case of confirmed uncomplicated malaria a patient with signs
and/or symptoms of uncomplicated malaria, who receives antima-
larial treatment, with laboratory confirmation of diagnosis.
Case of confirmed severe malaria a person requiring hospitali-
zation for signs and/or symptoms of severe malaria, who
receives antimalarial treatment, with laboratory confirmation of
diagnosis.
Confirmed malaria death death of a patient who has been
diagnosed with severe malaria, with laboratory confirmation of
diagnosis.
The signs and symptoms of malaria to be included in these definitions
may vary in different epidemiological settings (3). The uncomplicated
and severe malaria categories are intended to be mutually exclusive.
For example, a patient who initially presents with uncomplicated
malaria but then develops signs or symptoms of severe disease, should
only be classified as having severe malaria, and not counted twice.
This also applies to the probable and confirmed malaria categories.
Thus, countries would be expected to report probable and confirmed
cases separately.
Because of the increasing importance of antimalarial drug resistance
to malaria control efforts, standardized case definition is needed for
treatment failures:
Malaria treatment failure a patient with confirmed uncompli-
cated malaria with a history of having taken the correct dosage and
followed the regimen of the nationally recommended antimalarial
treatment, but who presents with asexual parasitaemia on a blood
smear within 14 days of the start of treatment.
47
9.1.2 Indicators
Once standardized case definitions have been agreed upon, indicators
can be developed to measure the progress of the control programme
(38). For the purpose of monitoring and evaluation, the indicators
should be closely linked to the programmes objectives. In deciding
how many indicators should be used, accurate measurement of a
small number of core indicators is preferable to imprecise measure-
ment of too many. As additional resources become available, and the
programme gains experience and makes progress, these indicators
can be refined, improved and added to. Most of the information
needed to measure the indicators can be obtained from three general
sources, although these sources may vary considerably in the quality
of data they provide. The information sources are:
1. Routine data collected by the national health-information system
(assuming that standardized case definitions have been agreed
upon and used, and these data are of acceptable quality).
2. Interviews and/or observations in health facilities. These could be
carried out during routine supervisory visits or during special
surveys.
3. Specific household or community surveys.1
The first two information sources should be available to all pro-
grammes; the third will require additional programme resources.
Although the cost of conducting such surveys may be high, savings
can be made by measuring several indicators in the same survey.
Core indicators
Although the choice of indicators must be left up to individual na-
tional programmes, the following core (impact and outcome) indica-
tors should be used in all malaria control programmes, irrespective of
their goals or the local epidemiological situation.
Impact indicators:
Morbidity attributed to malaria:
number of cases of uncomplicated malaria (probable and
confirmed) among target groups per unit population per unit
time;
number of cases of severe malaria (probable and confirmed)
among target groups per unit population per unit time.
1
Surveys may include specific questionnaires for assessing malaria control activities
carried out by the community.
48
Mortality attributed to malaria:
number of malaria deaths (probable and confirmed) among
target groups per unit population per unit time;
proportion of probable and confirmed malaria deaths among
patients with severe malaria admitted to a health facility per
unit time.
Malaria treatment failures number of microscopically confirmed
malaria treatment failures per number of patients treated. These
data should be reported for each drug used.
Outcome indicators:
Availability of antimalarial drugs percentage of health facilities
reporting no disruption of the stock of antimalarial drugs (as
specified in the national drug policy) during the previous 3 months.
Reporting of morbidity and mortality indicators percentage of
districts reporting morbidity and mortality indicators to the
national programme on a monthly basis during the previous 12
months.
Additional indicators:
The following additional indicators may be used, depending on the
epidemiological situation and the goals of the programme.
Annual parasite incidence (API) number of microscopically
confirmed malaria cases detected during 1 year per unit population.
Use of insecticide-treated mosquito nets proportion of target
groups provided with insecticide-treated nets and the proportion
that report that they slept under such a net the previous night.
These indicators will require household or community surveys and
are relevant to situations where the programme objectives are to
limit and prevent transmission of falciparum malaria.
Performance of mothers or carers proportion of mothers or
carers who ensure correct home management of children with
fever, in accordance with national policies. This indicator will
require household or community surveys.
Protection of pregnant women proportion of women in their first
and second pregnancies who report per unit time that they have
taken chemoprophylaxis or intermittent drug treatment, according
to national drug policies.
Preparation for malaria epidemics proportion of epidemic-prone
areas that have an epidemic containment plan and adequate stocks
49
of antimalarial drugs, supplies and functioning equipment in place
or easily accessible at least 1 month before the epidemic season
begins. This indicator is relevant to situations where the pro-
gramme objectives are to reduce mortality and morbidity, and to
limit transmission and prevent epidemics of falciparum malaria.
Intradomiciliary spraying of insecticides proportion of houses
sprayed per total number targeted for spraying. This indicator is
suitable for situations where the programme objectives are to limit
transmission and prevent epidemics of both falciparum and vivax
malaria.
Laboratory diagnosis:
proportion of health districts where quality control procedures
for malaria control are in place;
proportion of health facilities which have laboratory diagnostic
capabilities, from which an adequate sample of positive and
negative slides have been confirmed by a reference laboratory.
50
Operational research also has a part to play in the organization and
delivery of malaria control. Many malarious countries are in the
process of implementing economic and health sector reforms in which
individuals and communities are requested to increase their contribu-
tion to health services, while the provision of free health services is
reduced. Health services are also being decentralized to increase
community involvement. There is a need to consider how decentrali-
zation can be used to optimize malaria control activities and manage
community-based interventions.
51
Insufficient time for policy-makers, who are faced with urgent
problems of programme implementation, to evaluate research
results.
Insufficient national expertise to identify needs at the district level,
and to plan and implement operational research. Operational
research tends to be focused on urgent technical issues, such as
efficacy of drugs, insecticides and insecticide-impregnated materi-
als. Although there has recently been an increased focus on social,
economic and cultural issues, and health sector reform, local capac-
ity in these research areas is particularly limited.
Insufficient financial support at national and international levels to
support operational research. Research activities are rarely incorpo-
rated into and financed as part of national plans for malaria control,
relying instead on limited international and bilateral support.
Excessive delays in changing policies in the light of new research
and in the implementation of modified policies.
9.2.3 Addressing the constraints
Recently, there have been several initiatives to improve the coordina-
tion, implementation and funding of operational research, such as:
WHOs initiative (1996) for accelerated implementation of ma-
laria control in selected African countries;
a Multinational Initiative on Malaria (1997);
an East African Network (1997) funded from bilateral sources;
an Asian Collaborative Training Network for Malaria (1996) in
south-east Asia funded by WHO and other partners.
However, there is still an urgent need for WHO, and other partners,
to advocate that operational research should be incorporated into
and funded as part of all national plans of action for malaria control.
This would not only help to ensure that operational research is in line
with programme needs, but would also provide a system by which
programmes could commission urgent operational research for which
ministries of health do not, at present, have the funds.
The translation of results into practice would be facilitated at the
national level if national bodies were established and/or strengthened
to develop research priorities and strategies in line with control priori-
ties. They should provide a forum for bringing together, as partners,
researchers, health-care providers and policy-makers.
Tools for improving translation of results into practice are being
developed. Standard protocols are now increasingly being used in
operational research (3941). Information exchange is being facili-
52
tated by the development of several Web sites on the Internet, and
the production of an electronic register of controlled trials by the
Cochrane Infectious Disease Group (16, 4244; see Annex 2). While
access to computer-based information in malaria-endemic countries is
increasing, there is still a need to increase information exchange by
traditional means. In this context, WHO should publish relevant re-
search findings as rapidly as possible and should consider streng-
thening and expanding the Malaria Network Web site and Internet
discussion group recently established with World Bank support.
Translation of results into practice calls not only for increased dis-
semination of comparable research results, but also for those results
to be targeted to policy-makers and those responsible for implement-
ing control.
Training must be also an integral part of operational research inter-
ventions if national capabilities in operational research are to be
increased. Priority areas include:
development of research capabilities through hands-on involve-
ment in protocol development and implementation, and collection,
analysis and dissemination of results;
exchange of control programme staff between endemic countries
facing similar operational problems (e.g. staff from epidemic-prone
areas of one country assisting another during the outbreak of an
epidemic);
modification of university curricula for health workers to address
the practical needs of malaria control (e.g. aiming to increase their
awareness of information, education and communication needs of
the community and the patient, and the concepts of the Integrated
Management of Childhood Illnesses).
53
Improving disease management in the public and private sector. Re-
search issues include:
54
large-scale operational demonstrations of selective vector control;
evaluation of different options to reduce reliance on insecticides,
especially for indoor spraying.
Strengthening community involvement in malaria control
Research issues include:
understanding local perspectives and capacities for community-
based activities;
evaluation of different community-based approaches to determine
their impact (in terms of outcome and sustainability) on high-risk
groups, and their cost-effectiveness.
Strengthening national capacity to detect epidemics
Research issues include:
development of methods to predict, detect early and prevent
epidemics;
analysis of past and current epidemics, including meteorological
information, to identify causes of epidemics and develop appropri-
ate interventions to reverse or remove underlying factors and
define future actions.
Strengthening national capacity to plan, implement and evaluate malaria
control
Research issues include:
assessment of the impact of national health sector and economic
reforms on the implementation of malaria control;
management of the decentralization of control activities;
improvement of management and evaluation procedures at district
and national levels;
evaluation of the relevance of selected impact and outcome
indicators;
development and assessment of the impact of information, educa-
tion and communication materials.
55
11. Roll Back Malaria
The governments of malaria-endemic countries have identified ma-
laria as a high priority disease and there is growing political commit-
ment to control it. The Director-General of WHO, accepting the
challenge to lead the worlds efforts against malaria, has established
Roll Back Malaria (RBM), a WHO project to coordinate global
actions. RBM consists of a worldwide partnership, in which all part-
ners contribute their skills and resources to maximize the impact of
RBM on malaria control.
The main objective of RBM is to reduce the global malaria burden
significantly through interventions adapted to local needs and
strengthening of the health sector.
The basic concepts of the initiative are as follows:
RBM will address malaria as a priority health issue within the
context of health sector development that promotes intersectoral
collaboration and engages the community as partners.
WHO will provide strategic support to a global partnership in-
cluding organizations of the United Nations system (the United
Nations Childrens Fund and the United Nations Development
Programme), the World Bank, national governments of malaria-
endemic countries, bilateral donor agencies, nongovernmental
organizations and civil society.
WHO will work as a united institution by cutting across WHO
programmes within headquarters, regional and country offices to
tackle malaria.
RBM will achieve its objective by:
bringing reliable, sustainable prevention and early treatment to
affected populations;
investing in research and the development of effective and afford-
able tools;
building up human and institutional resources;
evaluating achievements against clearly defined targets.
The global partnership within RBM will:
support governments and country partnerships;
strengthen the health sector;
monitor the geographical spread of the disease and measure the
results of interventions;
improve technical efficiency and capacity by building and support-
ing technical and research networks in malaria-endemic countries;
56
coordinate efforts of country partnerships by promoting concerted
action and sharing information on malaria programmes, in order to
improve resource allocation and utilization.
RBM is a time-limited project (5 years). It will initially focus on
countries in Africa, south of the Sahara, where the malaria burden is
greatest and will be extended to include other regions of the world.
The preparatory phase has started: the first countries should be ready
to implement RBM plans and strategies by the year 2000.
The Expert Committee endorsed the technical basis of RBM and
welcomed the initiative as a further major development in the fight
against malaria.
57
malaria control. There is also a need to expand health services, par-
ticularly in Africa, south of the Sahara. Research and development
must be continued and strengthened to provide the new tools and
approaches required as the malaria situation changes. In the absence
of malaria vaccines with operational impact, new drugs are especially
required since the choice of drugs is limited and parasite resistance to
existing drugs is increasing. Furthermore, diagnostic tools must be
improved and made affordable. Thus, national governments and the
private sector should be made aware of the need to invest more in
malaria control efforts and of the importance of resources, to ensure
a reduction in malaria morbidity and mortality.
At present, one of the main priorities in all malaria control
programmes is training. Many countries lack the technical expertise
at central level to plan and evaluate the national programme, and
at the intermediate and peripheral levels to manage and implement it.
Many programmes do not possess adequate information systems
which are sufficiently sensitive, reliable and timely to identify emerg-
ing epidemics, and to sustain the logistic capacity required to provide
a rapid effective response. Particular attention must be given to train
personnel at the periphery. In Africa, south of the Sahara, steps
should be taken to train community members and health-care provid-
ers in the private sector.
Available information indicates that health sector reform varies from
country to country, but little is known of its impact on malaria control
programmes. The main concern is that indiscriminate decentraliza-
tion of all functions, from policy-making to programme implementa-
tion, should be avoided. There is a need to consider which functions
should be decentralized, as well as where, how and when this should
happen, along with careful planning and management of these
processes.
Although some additional funds to accelerate the implementation of
malaria control in the countries south of the Sahara have recently
become available, the needs still exceed the amount of money avail-
able. There is also no assurance that funding, at even the current level,
can be continued. Therefore, the initiative by the Director-General of
WHO to establish Roll Back Malaria is a welcome development. The
technical basis of this project is the Global Malaria Control Strategy.
Roll Back Malaria aims to cement a global partnership of malaria-
affected countries, United Nations organizations, bilateral develop-
ment agencies, nongovernmental organizations and the private
sector, all of which are committed to a common purpose and ways of
working together. The philosophy behind it is that malaria control can
58
only be successful if control is considered as part of sustainable na-
tional development.
12.2 Recommendations
12.2.1 General recommendation
Relevant WHO documents should be published as quickly as possible
in the appropriate WHO languages.
59
12.2.3 Disease management
1. Given that in many endemic areas, the available antimalarial drugs
are often substandard, ineffective, or sometimes only available too
far from where the disease occurs, greater efforts should be made
by national governments, health services and other partners to
ensure that all populations at risk have easy access to antimalarial
drugs which are of good quality, effective locally, affordable, and
formulated and packed to optimize patient compliance. Antima-
larial drugs should be accompanied by appropriate information.
2. In order to provide antimalarial drugs that are fully effective, safe,
affordable and easy to administer, and likely to remain so after
many years of use, pharmacokinetically compatible combinations
of artemisinin drugs and other effective schizonticides should, as a
matter of urgency, be developed, tested, and used in areas where
the therapeutic efficacy of chloroquine is no longer satisfactory.
3. In order to improve the quality of curative care in general and to
minimize the unnecessary use of antimalarial drugs, parasite detec-
tion tests (microscopical or immunological) should be made avail-
able as part of disease management at the periphery of health
services in endemic and epidemic-prone areas. The need for qual-
ity control, training, sustainability and costeffectiveness should
also be taken into account.
4. Given the increasing availability of a broadening range of anti-
malarial drugs and formulations from a variety of sources, it is
important that regulatory processes, drug quality control and qual-
ity assurance in endemic countries be improved and expanded by
strengthening national capabilities and by support from an interna-
tional network of technical resource centres. WHO and other in-
ternational agencies should consider establishing such a network.
5. Attention should be given to training in the management of severe
febrile disease in health services, including emergency measures at
the primary level as well as hospital care. It is essential that such
training is integrated into the broader clinical programmes, such as
malaria control programmes that are an integral part of health
sector reform.
12.2.4 Drug resistance
1. Monitoring of the efficacy of the recommended treatment options
for local falciparum malaria should be a regular activity of malaria
control programmes. Results of drug efficacy tests, together with
costs and other operational factors, should be used to update ma-
laria treatment guidelines as part of the national drug policy.
60
2. Coordinated by WHO, international monitoring of drug resistance
of P. falciparum should be established with the objectives of
analysing the long-term trends of the spread of parasite drug resist-
ance and sharing the information among countries. Analysis of
trends will serve to monitor, evaluate and guide drug utilization
strategies and other malaria control activities aimed at reducing or
preventing the selection of resistance.
61
part of antenatal care, should be made available in highly endemic
areas to women in their first and second pregnancies. Such inter-
mittent treatment should be started from the second trimester
onwards and should be given at intervals not less than 1 month
apart.
62
5. WHO should provide assistance to Member States in developing
appropriate mechanisms for improving the targeting of vector con-
trol interventions according to different epidemiological situa-
tions, taking into account various existing managerial structures
involved in malaria control. Integrated and selective vector con-
trol will reduce reliance on chemical insecticides and address
sustainability issues.
12.2.8 DDT
1. WHO, in its capacity of observer, should strengthen its active
engagement in the work of the Intergovernmental Negotiating
Committee, and call attention to the implications for malaria vec-
tor control of any type of regulation of DDT use that may be
proposed by a future Persistent Organic Pollutants Convention.
2. WHO should assist the appropriate vector control structures for
public health programmes of ministries of health in Member
States, through a process of consultation and information dissemi-
nation, to participate actively in the national activities related to
the work of the Intergovernmental Negotiating Committee leading
up to a future Persistent Organic Pollutants Convention.
3. It is anticipated that for some time to come there will continue to
be a role for DDT in combating malaria, particularly in the poorest
endemic countries. Restrictions on DDT for public health use
contained in a future Persistent Organic Pollutants Convention
should therefore be accompanied by technical and financial
mechanisms to ensure that effective malaria control is maintained,
to at least the same level, through vector control methods that
depend less on pesticides generally, and on DDT in particular.
12.2.9 Epidemics
1. The effectiveness of epidemic prevention and control is directly
proportional to the level of preparedness of the health services and
the functioning of the prediction system. Governments should give
full support to the strengthening or development of such services,
with the collaboration, if needed, of WHO and external agencies.
In particular, these services should identify and demarcate their
epidemic-prone areas, recognize the local determinants of epidem-
ics as well as risk indicators, and start the collection and analysis of
relevant data.
2. Collaboration mechanisms with other important sectors (e.g.
meteorological and agricultural services) should be established
to facilitate detection of epidemic risk. Malaria epidemiologists
63
should also support district medical officers in maintaining appro-
priate records and in guiding communities in the early detection
and control of malaria epidemics.
3. WHO should coordinate existing initiatives for early detection and
control of epidemics, as well as the appropriate use of information
and resources across interregional and international borders.
4. Countries with no or sporadic transmission should identify their
malaria-susceptible areas and monitor importation of malaria
cases in order to prevent re-establishment of transmission.
Acknowledgements
The Committee wishes to acknowledge the special contributions made during its
deliberations by the following: Dr K. Behbehani, Division of Control of Tropical
Diseases, WHO, Geneva, Switzerland; Dr A.E. Beljaev, WHO Regional Office for
the Eastern Mediterranean, Alexandria, Egypt; Dr F. Binka, Roll Back Malaria,
WHO, Geneva, Switzerland; Mr R. Bos, Division of Operational Support in
Environmental Health, WHO, Geneva, Switzerland; Dr A. Bosman, Malaria Control,
Division of Control of Tropical Diseases, WHO, Geneva, Switzerland; Dr M. Cham,
Malaria Control, Division of Control of Tropical Diseases, WHO, Geneva,
Switzerland; Mr J. Cheyne, Programme for Resource Mobilization, WHO, Geneva,
Switzerland; Dr M.R. Couper, Division of Drug Management and Policies, WHO,
Geneva, Switzerland; Mr A.L. Creese, Division of Analysis, Research and
Assessment, WHO, Geneva, Switzerland; Dr C. Delacollette, Malaria Control,
Division of Control of Tropical Diseases, WHO, Geneva, Switzerland; Dr H. Engers,
Product Research and Development, UNDP/World Bank/WHO Special Programme
for Research and Training in Tropical Diseases, WHO, Geneva, Switzerland; Dr D.
Evans, Global Programme on Evidence for Policy, WHO, Geneva, Switzerland; Dr
T. Godal, Roll Back Malaria, WHO, Geneva, Switzerland; Dr R.J. Guidotti, Division
of Reproductive Health, Maternal and Newborn Health/Safe Motherhood, WHO,
Geneva, Switzerland; Dr R. Gusmo, WHO Regional Office for the Americas/Pan
American Sanitary Bureau, Washington, D.C., USA; Mr G. Hartl, Communicable
Diseases, WHO, Geneva, Switzerland; Dr P. Herath, Malaria Control, Division of
Control of Tropical Diseases, WHO, Geneva, Switzerland; Dr D.L. Heymann,
Communicable Diseases, WHO, Geneva, Switzerland; Dr H.M. Kahssay, Division
of Intensified Cooperation with Countries and Peoples in Greatest Need, WHO,
Geneva, Switzerland; Dr Y. Kassankogno, WHO Regional Office for Africa, Harare,
Zimbabwe; Dr J. Liljestrand, Division of Reproductive Health, Maternal and
Newborn Health/Safe Motherhood, WHO, Geneva, Switzerland; Dr S. Lwanga,
Strengthening Country Health Information, WHO, Geneva, Switzerland; Dr L.
Manga, WHO Regional Office for Africa, Harare, Zimbabwe; Dr. K.N. Mendis, Roll
Back Malaria, WHO, Geneva, Switzerland; Dr C. Morel, UNDP/World Bank/WHO
Special Programme for Research and Training in Tropical Diseases, WHO,
Geneva, Switzerland; Dr M. Nathan, Filariasis Control, Division of Control of
Tropical Diseases, WHO, Geneva, Switzerland; Dr P.L. Olliaro, Product Research
and Development, UNDP/World Bank/WHO Special Programme for Research and
Training in Tropical Diseases, WHO, Geneva, Switzerland; Dr V.S. Orlov, WHO
Regional Office for South-East Asia, New Delhi, India; Dr A. Rietveld, Malaria
Control, Division of Control of Tropical Diseases, WHO, Geneva, Switzerland; Dr A.
Robb, WHO Regional Office for Africa, Harare, Zimbabwe; Dr D. Robinson,
Division of Child Health and Development, WHO, Geneva, Switzerland; Dr G.
64
Sabatinelli, WHO Regional Office for Europe, Copenhagen, Denmark; Dr A.
Schapira, Office of the WHO Representative in the Socialist Republic of Viet Nam,
Hanoi, Viet Nam; Dr A. Teklehaimanot, Malaria Control, Division of Control of
Tropical Diseases, WHO, Geneva, Switzerland; Dr P. Trigg, Malaria Control,
Division of Control of Tropical Diseases, WHO, Geneva, Switzerland; Dr O. Walker,
WHO Regional Office for Africa, Harare, Zimbabwe; Mr K. Woldeyesus, Action
Programme on Essential Drugs, WHO, Geneva, Switzerland; and Dr M. Zaim, WHO
Pesticide Evaluation Scheme, Division of Control of Tropical Diseases, WHO,
Geneva, Switzerland.
The Committee also expresses its thanks to Professor M.E. Molyneux and Dr D.
Payne for their contribution to the discussions through their working papers.
In addition, the Committee would like to express its gratitude to Ms J. Curry for
organizing the meeting and to Mrs J. Griffith and Mrs P. Griffiths for providing
support services.
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10. Beadle C et al. Diagnosis of malaria by detection of Plasmodium falciparum
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diagnosis of malaria. Annals of tropical medicine and parasitology, 1998,
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38. Information systems for the evaluation of malaria control programmes: a
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Annex 1
Use of DDT in vector control1
The WHO Study Group on Vector Control for Malaria and Other
Mosquito-Borne Diseases considered the current situation regarding
the use of DDT for controlling vector-borne diseases, in particular
malaria, in the light of two recent publications suggesting an associa-
tion between DDT and human cancers (1, 2), a report on the presence
of DDT in breast milk (3), and two general reviews of the subject.2
Two expert toxicologists3 were invited to review these papers, includ-
ing the citations, and to participate in the discussions on DDT.
After careful review of the documents and intensive discussion, the
Study Group concluded that:
1. The information presented does not provide convincing evidence
of adverse effects of DDT exposure as a result of indoor residual
spraying as carried out in malaria control activities.
2. There is therefore, at this stage, no justification on toxicological or
epidemiological grounds for changing current policy (4) towards
indoor spraying of DDT for vector-borne disease control.
3. DDT may therefore be used for vector control, provided that all
the following conditions are met:
(a) it is used only for indoor spraying;
(b) it is effective;
(c) the material is manufactured to the specifications issued by
WHO (5);
(d) the necessary safety precautions are taken in its use and
disposal.
4. In considering whether to use DDT, governments should take into
account the following additional factors:
(a) the costs involved in the use of insecticides (DDT or
alternatives);
(b) the role of insecticides in focal or selective vector control, as
specified in the Global Malaria Control Strategy (6, 7);
(c) the availability of alternative vector control methods, in-
cluding alternative insecticides (in view of the availability of
1
Reproduced, with minor editorial changes, from Vector control for malaria and other
mosquito-borne diseases. Report of a WHO Study Group. Geneva, World Health
Organization, 1995 (WHO Technical Report Series, No. 857).
2
Prepared by: Dr C.F. Curtis, Department of Medical Parasitology, London School of
Hygiene and Tropical Medicine, London, England; and Professor J. Mouchet, French
Institute for Cooperative Scientific Research for Development (ORSTOM), Paris, France.
3
Dr W.N. Aldridge, The Robens Institute, University of Surrey, Guildford, England; and
Professor M. Lotti, Institute of Occupational Medicine, University of Padua, Padua, Italy.
69
alternative insecticides for indoor residual spraying, some of
which may compete with DDT in terms of epidemiological
impact, public acceptability, logistic suitability and compliance
with specifications issued by WHO, DDT no longer merits
being considered the only insecticide of choice);
(d) the implications for insecticide resistance, including possible
cross-resistance to some alternative insecticides;
(e) the changing public attitude to pesticide use, including public
health applications.
5. Given the paucity of data suggesting adverse effects of indoor
house-spraying, further epidemiological investigation using rigor-
ous scientific protocols is to be encouraged.
6. Further studies should also be carried out to:
(a) examine the health effects of DDT in breast milk on breastfed
infants, including any resulting behavioural change;
(b) investigate thoroughly any suspected association between the
use of DDT in routine malaria control activities and an
increased incidence of cancer(s);
(c) clarify the significance of the reduction in muscarinic receptor
density caused by DDT.
References
1. Garabrant DH et al. DTT and related compounds and risk of pancreatic
cancer. Journal of the National Cancer Institute, 1992, 84:764771.
2. Wolff MS et al. Blood levels of organochlorine residues and risk of breast
cancer. Journal of the National Cancer Institute, 1993, 85:648652.
3. Bouwman H et al. Levels of DDT and metabolites in breast milk from
Kwa-Zulu mothers after DDT application for malaria control. Bulletin of the
World Health Organization, 1990, 68:761768.
4. The place of DDT in operations against malaria and other vector-borne
diseases. In: Executive Board Forty-seventh Session, Geneva, 1929 January
1971, Part II. Report on the proposed programme and budget estimates for
1972. Geneva, World Health Organization, 1971 (Official Records of the
World Health Organization, No. 190):176182.
5. Specifications for pesticides used in public health, 7th ed. Geneva, World
Health Organization, 1997 (unpublished document WHO/CTD/WHOPES/97.1;
available on request from the Documentation Centre, Communicable
Diseases, World Health Organization, 1211 Geneva 27, Switzerland).
6. A global strategy for malaria control. Geneva, World Health Organization,
1993.
7. Implementation of the Global Malaria Control Strategy. Report of a WHO
Study Group on the Implementation of the Global Plan of Action for Malaria
Control 19932000. Geneva, World Health Organization, 1993 (WHO
Technical Report Series, No. 839).
70
Annex 2
Improving information exchange
There have been several initiatives in recent years to increase the
rapid exchange of information on malaria. These include the:
Malaria Network, a Web site and Internet discussion group estab-
lished in June 1998 by WHO in collaboration with the World Bank.
This is aimed at malaria control managers, ministry of health staff
and other health workers with special responsibilities for the imple-
mentation of malaria control. It provides technical and managerial
information relevant for malaria control activities in the field and
functions as a forum for discussion. The network is demand-driven,
and is regularly adapted to the identified needs of the target user-
groups. Web site: http://www.malarianetwork.org.
Malaria Foundation International: Global Networking Against
Malaria. Founded in 1992 to facilitate the development and imple-
mentation of solutions to the health, economic and social problems
caused by malaria, by supporting global communication and net-
working, research, education and training. The Web site includes
databases on the malaria research network and malaria genome,
and provides updated information on all aspects of malaria and its
control. Web site: http://www.malaria.org.
Multilateral Initiative on Malaria (MIM) Newsletter, published
by the Wellcome Trust since mid-1998 to provide information on
the current activities of the Initiative. It is also available on the
Wellcome Trusts Web site: http://www.wellcome.ac.uk.
Asian Collaborative Training Network for Malaria (ACTMalaria)
Web site. The ACTMalaria newsletter is available at this site: http:
//www.actmalaria.org.
Environmental Health Project, which has a special bibliography of
malaria-related articles, including publications on bednets. Web
site: http://www.access.digex.net/~ehp/webliog-html.
Cochrane Infectious Disease Group maintains an electronic register
of controlled trials, available on CD-ROM and diskette. Cochrane
library Web site: http://www.updateusa.com/clibip/clib.htm.
71
World Health Organization Technical Report Series
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843 (1994) Assessment of fracture risk and its application to screening for
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Report of a WHO Study Group (134 pages) 22.
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i
Despite considerable progress in malaria control over the past
decade, malaria remains a serious problem particularly in
Africa, south of the Sahara, where about 90% of clinical cases
occur. Malaria, either alone or in combination with other dis-
eases, is estimated to kill between 1.1 and 2.7 million people
worldwide each year, and over 2400 million remain at risk.
This report of a WHO Expert Committee reviews the progress
made since 1992 in the implementation of the Global Malaria
Control Strategy and analyses the effect of health sector re-
forms on malaria control programmes. The importance of more
recent initiatives, such as the Roll Back Malaria project, is also
discussed.
The report focuses on disease management and on drug
resistance of malaria parasites, one of the greatest challenges
currently facing control programmes. Guidance is given on how
to predict, prepare for, control and prevent malaria epidemics,
which threaten large areas of the world.
The use of chemoprophylaxis and selective vector control in the
prevention of malaria is discussed. As accurate epidemiological
information is essential for assessing public health needs and
for monitoring malaria control programmes, a number of stan-
dardized case definitions and indicators have been developed.
In order to make programme activities effective and responsive
to changing epidemiological situations, the report emphasizes
the need for operational research at a national level.
Although existing tools have had an impact on malaria morbidity
and mortality, it is clear that much remains to be done. The
report concludes with a list of recommendations to ensure that
the present achievements are sustained and that a greater
impact is made on the disease, particularly in Africa.
ii