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CLINICAL MICROBIOLOGY REVIEWS, Apr. 2002, p. 278–293 Vol. 15, No. 2
0893-8512/02/$04.00⫹0 DOI: 10.1128/CMR.15.2.278–293.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Integrated Approach to Malaria Control
Clive Shiff*
The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg
School of Public Health, Baltimore, Maryland 21205
INTRODUCTION .......................................................................................................................................................278
GLOBAL STRATEGY FOR MALARIA CONTROL .............................................................................................279
Background..............................................................................................................................................................279
Decentralization of Health Services .....................................................................................................................280
Past Achievements ..................................................................................................................................................280
Clouds on the Horizon ...........................................................................................................................................281
BASIC CONCEPTS OF MALARIA CONTROL ....................................................................................................281
Biological Basis .......................................................................................................................................................281
Strategies for Control.............................................................................................................................................282
Mortality control.................................................................................................................................................282
Transmission control..........................................................................................................................................283
Eradication of malaria .......................................................................................................................................283
TOOLS TO CARRY OUT MALARIA CONTROL ................................................................................................283
Personnel and Strategy Development ..................................................................................................................283
Environmental Management .................................................................................................................................284
Intradomicile Application of Residual Insecticides ...........................................................................................284
Application...........................................................................................................................................................285
Selection of insecticides .....................................................................................................................................285
Planning ...............................................................................................................................................................285
Insecticide-Treated Mosquito Nets.......................................................................................................................285
TECHNIQUES FOR IMPLEMENTATION OF ITN PROGRAMS ....................................................................286
Finance and Subsidy ..............................................................................................................................................286
Reimpregnation .......................................................................................................................................................287
Sustaining the Intervention...................................................................................................................................287
STRATEGIES BASED ON BIOLOGICAL CHARACTERISTICS OF MALARIA TRANSMISSION ...........287
Barrier Spraying .....................................................................................................................................................287
Structured Malaria Control ..................................................................................................................................289
Evaluation of Efficacy .............................................................................................................................................289
INSECTICIDES, INSECTICIDE RESISTANCE, AND MALARIA CONTROL ...............................................289
DIAGNOSIS OF INFECTION..................................................................................................................................290
TRAVEL MEDICINE AND PROBLEMS DUE TO GLOBAL CLIMATE CHANGE.......................................290
MALARIA VACCINES...............................................................................................................................................291
FINALE: ROLL BACK MALARIA...........................................................................................................................291
ACKNOWLEDGMENTS ...........................................................................................................................................291
REFERENCES ............................................................................................................................................................291
INTRODUCTION
When one looks over the global distribution of malaria in
the 21st century, it is difficult to realize how widespread the
disease has been and how its distribution has diminished dur-
ing the past 150 years. This is important because in many
places it may have the potential to return if appropriate cli-
matic conditions prevail. Historically, malaria fever (ague) was
reported in one form or another from parts of southern and
eastern England and seasonally in Holland, Germany, across
central and southeastern Europe, much of Asia, India, China,
almost all the Americas, and of course most tropical regions
(20). In North America the disease existed in large areas ex-
tending as far north as New York and even Montreal (15).
During the U.S. Civil War, possession of quinine was vital for
the warring forces to ensure that large numbers of the men
were not incapacitated by the disease (107). During the mid-
19th century, evidence of malaria became more sporadic and
the disease receded from most of central Europe although it
remained entrenched in the Mediterranean region and the
Balkans (85). In the United States, major modifications of
mosquito habitat through the Tennessee Valley Authority ma-
laria control program, habitat degradation, deforestation,
flooding, and other effects of development restricted the hab-
itat of the malaria mosquito Anopheles quadrimaculatus and
led to the local decline of malaria (33). Its eventual disappear-
ance was probably due to improvements in life-style, screened
housing, and the eventual absence of the reservoir within the
human population. During that period, the prevalence of ma-
laria in temperate areas of Europe was declining without spe-
* Mailing address: The W. Harry Feinstone Department of Molec-
ular Microbiology and Immunology, Johns Hopkins Bloomberg School
of Public Health, 615 N. Wolfe St., Baltimore, MD 21205. Phone: (410)
955-1263. Fax: (410) 955-0105. E-mail: cshiff@jhsph.edu.
278
cial efforts (85), while in southern Europe and Turkey, where
the disease was more endemic, elimination was achieved with
the advent of DDT. Expanded mosquito control programs
during the period from 1950 to 1970 finally brought success in
many parts of the world through the concerted efforts of the
World Health Organization (WHO) (47). (Table 1)
In spite of these successes, the fabric of many of these
expanded control programs began to unravel during the early
1970s. The appearance of mosquitoes resistant to DDT and
other residual insecticides (12), as well as the extreme difficul-
ties involved in the supervision and financing of the various
programs, led to problems which became overwhelming. This
can be seen in Sri Lanka, a country with high levels of epidemic
transmission in the past. During an epidemic in 1934, 60,000
new cases were being reported daily (19). Malaria eradication
commenced in Sri Lanka in 1947, and in 1963, at the height of
the eradication programs, only 17 cases were recorded through-
out the country. Mass population movements into forested
areas and the withdrawal of intradomicilary spraying with
DDT due to the advanced level of control achieved (i.e., tran-
sition from attack phase to consolidation phase) contributed to
faltering control, and in 1969, over 500,000 cases were reported
in the country (42). This situation was not unique. Numerous
other problems arose because of inadequate field research and
also because eradication was a concept dreamed up by over-
enthusiastic authorities who showed little flexibility in their
drive for completion of the plans (57).
Even in temperate countries from which malaria has disap-
peared, the vector mosquitoes still exist as a sort of biological
time bomb. Particularly with the threat of global climate
change, all that is required is the reintroduction of sufficient
numbers of gametocyte carriers for the disease possibly to start
up again in epidemic proportions (67).
At the advent of the new millennium, malaria continues to
plague mankind as a burgeoning problem without any signs of
abatement (47). The current world malaria situation is proba-
bly no better that it was 30 years ago, when the emphasis on
eradication was replaced by a somewhat defeatist holding pro-
gram (121). This new strategy allowed countries to adopt less
than effective “control” programs, many which were based
entirely on the distribution of the cheap, effective drug chlo-
roquine. This has resulted, in part at least, in a series of prob-
lematic situations which eventually led to the breakdown in
health services and the loss of skilled personnel dedicated to
the study and control of malaria in areas of endemic infection.
Additionally, there were biological problems which arose from
widespread resistance of the parasite to the most effective and
best-tolerated drugs and selection of vector mosquitoes which
became resistant to many available insecticides.
WHO has attempted to address this deteriorating situation
by holding a ministerial-level conference to develop a strategy
to address malaria (123). This culminated in the global strategy
for malaria control entitled “Roll Back Malaria,” which is now
in the process of implementation. The strategy, which is not
without critics (12) was developed mainly to address African
conditions, where malaria is most serious. One of the arms of
this approach calls for the use of antimalarial drugs in an
almost unrestricted basis through clinics and health centers
and even in the home following simple diagnosis. There is little
emphasis on an integrated approach to malaria control (Table
2).
GLOBAL STRATEGY FOR MALARIA CONTROL
Background
Attitudes regarding malaria during the past century have
fluctuated between hope during periods when worldwide con-
trol seemed in reach, and despair as problems seemed to
mount in spite of massive research efforts. For the most part,
research thrusts have focused on the development of new
drugs and vaccines (7), with decreasing emphasis on conditions
in the field (124). Now, with the advent of the new century, we
are faced with a situation which in many ways is far worse than
in the 1950s, when the plans for eradication were first intro-
duced (119). Countries where infection is endemic have lost
much of the infrastructure which could be used to mount a
systematic attack on the parasite and its transmission. Parasite
resistance to available antimalarials is spreading and has ren-
dered treatment increasingly difficult for most people exposed
to infection (116). In some instances, the possibility of untreat-
able multidrug-resistant malaria looms precariously (12).
TABLE 1. People affected by malaria eradication
a
WHO region
Total
b
no. of
affected
persons
No. of persons affected in:
Areas with no malaria
or from which it
disappeared without
specific measures
Areas originally
with malaria
Areas where malaria
eradication was
claimed
Areas where eradication programs were in progress
in 1966
Consolidation
phase
Attack phase
Preparatory
phase
Total
Africa 212,883 16,318 196,595 3,223 2,733 490 3,223
Americas 463,355 308,845 154,510 61,926 40,831 38,737 12,811 92,379
South-east Asia 689,123 39,278 649,845 174,983 281,111 153,311 6,531 440,953
Europe 739,311 409,207 330,104 269,536 29,946 9,224 39,170
Eastern Mediterranean 238,009 60,207 177,802 6,459 11,339 57,900 24,017 93,256
West Pacific 232,316 165,190 67,126 18,880 4,288 5,336 9,624
Total 2,574,997 999,045 1,575,952 535,007 370,248 264,998 43,359 678,605
a
As of 31 December 1965. Data given by region, excluding China, North Korea, and North Vietnam. Table adapted from reference 129 with permission of the
publisher. WHO, World Health Organization.
b
United Nations demographic.
VOL. 15, 2002 INTEGRATED APPROACH TO MALARIA CONTROL 279
During the past 40 years or so, major decisions were made
which guided the world body in its quest to attack malaria and
to address the overall health programs in developing nations
(48). Successes with vaccines against other diseases prompted
research to focus on the development of antimalaria vaccines
(81). The research effort has helped us to learn much about the
disease and its epidemiology as well as the nature and molec-
ular biology of malaria parasites; however, the task of devel-
oping a vaccine has remained daunting. Only now are we
beginning to investigate the genetic diversity among popula-
tions of malaria parasites (11). Such studies will help us to
understand more about the extent of parasite variability, which
may impact not only on the way the disease is expressed but
also on how immunity may develop in the human population.
This information will greatly affect the strategy of vaccine de-
velopment and its use.
Decentralization of Health Services
In the meantime, the ability to control malaria has deterio-
rated in countries with endemic infection (106). Within these
countries, major donors of aid have directed efforts toward
promotion of decentralization of health programs, not specif-
ically to handle malaria but to provide more services to the
rural poor. The process of decentralization has had an insidi-
ous effect on the local infrastructure as the technical support
for such developing nations to attack malaria, or even to de-
velop rationally planned control interventions, has been eroded
(48). Whereas the concept of decentralization is an appropri-
ate basis for dispersing meager health services to the periph-
ery, particularly in rural areas, when a professional scientific
body of experts is somehow decentralized the result can be
devastating. As with all scientific endeavour, a critical mass of
experts is needed to facilitate the work. If these units are
broken up and decentralized, the professional interaction is
lost and the staff eventually will seek other, more stimulating
activities, leading to a brain drain. Moreover, these staff cannot
easily be replaced, particularly in the atmosphere of decreasing
salaries and bureaucratic deterioration seen in these countries.
The study of malaria and its epidemiology and control is a
highly technical enterprise, requiring a body of experienced
scientists to maintain oversight and efficient monitoring of the
local situations. Without these personnel, ministries of health
are not able to formulate rational malaria control strategies
and hence become dependent on imported technical advisors
who are usually unfamiliar with local conditions and whose
advice may not be appropriate (103). It becomes difficult for
the ministries to plan effectively for the efficient use of dwin-
dling resources, and conditions then deteriorate to the crisis
situation we now observe. In the light of this state of affairs,
one needs to consider the various options available to malaria-
endemic nations to control malaria in the most effective man-
ner in their own ecological regions. Hopefully, it is for others
to consider the hurdles that have been placed before these
nations so that appropriate help may be given in the immediate
future.
Past Achievements
Malaria control as propounded by various expert commit-
tees on malaria was a successful enterprise in many ways. It is
frequently forgotten that by 1966 malaria eradication programs
globally had freed some 525 million people (34% of the pop-
ulation living in previously malarious areas) from the threat of
this disease (Table 1). In the Americas, concerted malaria
control efforts, using both vector control and treatment, had
achieved great success, with massive declines in infection being
seen throughout the region (21). The successful attacks on
malaria produced a strong infrastructure of personnel. Well-
trained cadres of malaria control specialists were employed
and carried out regular house spraying, treatment of cases
detected by active surveillance, and collection of statistics for
TABLE 2. Global strategy for malaria control
a
Item Technical elements (WHO 1993) Implementation objectives Caveat
1 Provide early diagnosis and prompt
treatment
Develop paradigms for presumptive
diagnosis by mothers or rural
health workers; provide
treatment in home and clinic
(120)
Difficult to implement, particularly when
second-line drugs are required. Many
false positives (10, 35)
2 Plan and implement selective and
sustainable preventive measures,
including vector control
Expand use of ITN’s, encourage
partnerships, train personnel
Lack of national implementation strategies
may lead to disjointed programs; some
partners have specific goals (e.g.,
UNICEF concentrates on pregnant
women and children under 5 yr); this is
not malaria control; regular change of
personnel
b
3 Detect, contain or prevent
epidemics
Develop epidemiological
surveillance
4 Strengthen local capacities in basic
and applied research to permit
and promote the regular
assessment of a country’s malaria
situation, in particular the
ecological, social, and economic
determinants of the disease
Provide training opportunities for
local scientists, regular planning
on regional basis
Few training opportunities occur in
countries with endemic infection also
difficult to provide satisfactory career
opportunities leading to a brain drain
b
a
Adopted by Ministerial Conference, October 1992 (120).
b
Points of discussion at the July meeting of the WHO-Southern African Malaria Control programme, Victoria Falls, Zimbabwe, 22 to 29 July 2001.
280 SHIFF CLIN.MICROBIOL.REV.
assessment of the effects (50). In 1959, the Annual Parasite
Index (the number of positive blood slides per 1,000 popula-
tion) for the whole region of Latin America was 0.39. Sadly, by
1996 the Annual Parasite Index had increased eightfold and
was 2.46 for the region; for people living in malarious areas, it
was 12.5 (21).
Clouds on the Horizon
By 1966 the problem of anopheline resistance to DDT had
become clear. There were 15 species resistant to DDT and 36
resistant to dieldrin (127); equally important, chloroquine re-
sistance was reported in Southeast Asia and South America
(120). Although eradication programs had achieved consider-
able success (Table 1), the WHO Expert Committee in 1968
adopted a definition that “Areas with technical problems are
those where the planned single or combined attack measures
correctly applied have failed to interrupt transmission.” By
1973, the changes in programs were extensive, with a totally
new approach developed based on implementation of so-called
tactical variants, which identified a series of levels under which
control programs should operate. These ranges from a reliance
on chemotherapy alone to reduce mortality (Tactical Variant
1) to a reliance mainly on chemotherapy and limited protection
factors for reduction and prevention of mortality and morbid-
ity, particularly in high-risk groups (Tactical Variant 2). Fi-
nally, with Tactical Variant 4, countrywide malaria control was
the ultimate objective (120, 121). This change of strategy began
the decline in many national malaria control programs. The
effect of this on the control programs in the Americas has been
disastrous—a profound decrease in house spraying and a de-
pletion of trained operatives has resulted in an upsurge in
malaria (21, 45) To illustrate, 1,500 cases were reported from
Loreto Province in Peru in 1965 while 121,268 cases occurred
in 1997 (44).
WHO surveillance has revealed that areas of western Asia,
Armenia, Azerbaijan, and Tajikistan from which malaria had
been eradicated in the 1960s had started to report cases of
malaria, with several thousand cases occurring in 1994 (12,
126). Similar increases have been reported in Turkey (126) and
Iraq (126); more recently, in South Korea there has been a
logarithmic increase in vivax malaria between 1993 and 1997
(36). The reasons for this are difficult to summarize, but un-
derlying the situation is a loss of international drive to consider
the malaria problem holistically, and part of that is the design
behind the Global Strategy for Malaria Control (12).
In a well-reasoned argument, Baird (12) supports the mes-
sage of Butler and Roberts (21) and has delivered a warning to
public health administrators. Both authors think that the two
factors which contributed most significantly to the past control
and reduction of malaria were (i) the use of DDT as an indoor
spray to attack the vector mosquitoes and (ii) the widespread
use of chloroquine as an effective chemotherapeutic. The
emergence of chloroquine resistance and the deterioration of
national control programs that applied DDT (and other insec-
ticides) have been coincident with the upsurge of malaria.
Currently, the Global Strategy for Malaria Control, which was
designed as a lifeline for Africa (Table 2), emphasizes early
diagnosis and prompt treatment as the major line of attack.
While this is appropriate for immediate survival of severe
cases, there is no evidence that it will effectively reduce the
transmission of malaria. Lack of emphasis of the role of vector
control as an intervention against malaria has restricted inte-
grated approaches to malaria control (106). Authorities (12,
21) feel that this strategy is setting the stage for further spread
and increase of malaria, not only because it deemphasizes
vector control but also because it inevitably leads to misuse of
drugs (home diagnosis and treatment), which will lead to an
increase in parasite resistance and further escalation of the
malaria problem (10, 35, 94).
In light of these warnings, it is pertinent now to examine the
tools available for malaria control and consider how they may
be used in an integrated approach to regulate this reemerging
problem of malaria in the new millennium.
BASIC CONCEPTS OF MALARIA CONTROL
Biological Basis
Malaria is a focal disease with extremely varied epidemiol-
ogy based largely on the reservoir, which may or may not be
asymptomatic, and the biting patterns and vectorial capacity of
the vector mosquitoes. Initially, this complex relationship was
not well understood, and after the discoveries by Grassi and
Ross of the role of mosquitoes in the parasite cycle (20), these
insects became the main target of control efforts (85). In the
absence of methods to kill adult mosquitoes, the strategy was
to reduce breeding sites. Accordingly, a considerable effort was
made to drain swamps and marshes and to somehow limit the
populations of mosquitoes, whether vectors or not. The Pon-
tine marshes near Rome and the Hula swamps in Israel are
often used as examples of success in eliminating vector popu-
lations (33). However, as pointed out by White these examples
were not necessarily applicable elsewhere (118). The Sardinian
project (1946 to 1951) against Anopheles labranchiae confirmed
that it was difficult to eradicate an endemic vector by system-
atic larvicide application or, even when insecticides were avail-
able, by targeting adults by house spraying (58, 85). The point
is that if eliminating mosquito vectors is not an option, what
then can be done?
Macdonald concentrated on mathematical models of ma-
laria transmission and foresaw the importance of the prepatent
period within the infected mosquito (61). Subsequently, by
estimating the duration of prepatency in a mosquito after its
infective blood meal and the variable life span of female
anopheline mosquitoes, he reasoned that transmission could
be interrupted by reducing mosquito survival to less than the
duration of sporogony (the mosquito stage of the parasite
leading to the production of infective sporozoites). He sug-
gested that this would be more effective in controlling trans-
mission than merely reducing the mosquito density (61). This
is, in fact, the main reason why indoor spraying is far superior
to larvicide application or space spraying to attack the mos-
quito populations. To explain this concept, it is necessary to
understand vectorial capacity.
Vectorial capacity (C)defines the efficiency of a mosquito
species to act as a vector of the malaria parasite. It is expressed
by the formula C ⫽ ma
2
p
n
/⫺log
e
p (38, 39), where C is vecto-
rial capacity, m is the relative density of female anopheline
mosquitoes to humans, a is the probability that a mosquito will
VOL. 15, 2002 INTEGRATED APPROACH TO MALARIA CONTROL 281
feed on a human in a day, ma is the number of times a person
is bitten per day, p
n
is the proportion of the vector population
that survives the incubation period of the parasite in the mos-
quito, and 1/⫺log
e
p is the number of days that this proportion
is expected to survive. The formula defines the critical role of
the vector in determining the incidence of infection in any
community and supports the theory behind indoor use of con-
tact insecticides or insecticide-impregnated bed nets. It calcu-
lates the actual level of transmission as well as the epidemiol-
ogy and pattern of illness seen in communities with endemic
infection (89). In this expression, p
n
greatly outweighs the
importance of mosquito density in relation to humans (ma).
Thus, for the purpose of limiting transmission, it is more ef-
fective to reduce mosquito longevity than to reduce mosquito
density (118).
This point needs to be reiterated continuously because it is
forgotten frequently by those who recommend source reduc-
tion, “environmental management,” and other ill-defined con-
cepts (93) which serve little purpose other than to deflect
scarce resources to abating populations of nuisance mosqui-
toes. It is interesting that as early as 1931, systematic house
spraying with pyrethrum was introduced (53). The concept was
“not intended to destroy all Anopheles gambiae, but only those
which are infected. . .largely to be found indoors” (118).
The duration of mosquito survival after an infective bite
forms the fundamental basis for the use of indoor spraying or
of insecticide-impregnated bed nets to control transmission.
The duration of sporogony, the period following ingestion of
infective gametocytes by a susceptible mosquito prior to the
maturation of sporozoites and their migration to the salivary
glands, is dependent on the prevailing temperature conditions.
For Plasmodium falciparum, sporogony development in the
mosquito is inhibited when the ambient temperature falls be-
low about 20°C and lasts approximately 10 days at tempera-
tures between 25 and 30°C. With P. vivax, development is more
rapid at the higher temperature (approximately 6 days) but
proceeds, although slowly, even at temperatures around 16°C
(61). With all blood-fed mosquitoes, and particularly members
of the genus Anopheles, the females become heavy and vulner-
able after a feed, flying to a nearby surface, where they rest and
commence digestion (40). Usually the meal is taken during the
night, and the mosquitoes will seek a secluded corner or hard
surface as a refuge. If this surface is treated with insecticide,
the mosquito may acquire a lethal dose. However, even if only
a partial (sublethal) dose is acquired, the mosquito may survive
but must take a blood meal every 2 to 3 days in order to
accomplish oviposition and ensure survival of the species.
Thus, before a mosquito can transmit malaria parasites, it will
very probably return to feed two or three times, and at each
occasion it is vulnerable to exposure to insecticide. The role of
the insecticide applied to the walls of a hut, room, or mosquito
net is not necessarily to kill the mosquito immediately but to
provide a sufficient dose to kill the mosquito before the infec-
tion becomes patent (41). In spite of the current high level of
research into the biology of the malaria parasite, control of
malaria transmission for the foreseeable future will continue to
depend on these basic principles.
Strategies for Control
Malaria control is too complex to be addressed by a single
approach, and any attempt to do so is fraught with danger. It
is important to tailor the strategy to the prevailing ecological
and epidemiological conditions (78). To illustrate this, defini-
tions of the four main patterns of epidemiology (Table 3) are
based on indicators which can be measured in the community.
Of significance, the immune status of the population and the
patterns of malaria seen will be different in these four situa-
tions and will also affect the strategy for control. Therefore,
these will be dictated by the prevailing transmission patterns
and will be orientated to the following outcomes: (i) mortality
control, (ii) transmission control, and (iii) eradication.
Mortality control. The major impact of malaria in any com-
munity is that of the death of individuals. To prevent a person
dying from the disease, appropriate treatment is necessary.
The strategy of mortality control involves detecting presump-
tive cases, determining which cases are parasite positive, and
administering effective treatment. Such a strategy has little
impact on morbidity due to malaria and has little or no effect
on the overall transmission of the disease. In areas of holoen-
demic infection, this morbidity results in a major burden on the
population (66).
Mortality control is the main thrust of the current “Global
Malaria Control Strategy” (Table 2) (123). Since it relies on
chemotherapy, no particular program is required, nor is there
any need for nationwide strategies and the development of
local priorities. All that is required is some means for record
keeping and a system for distribution of the drugs of choice to
TABLE 3. Classification of levels of endemicity of malaria transmission
Endemicity level Transmission Parasite rate (%)
a
Comment
Hypoendemic malaria Low: subperiodic or sporadic Usually ⬍10% Mosquito populations unstable, usually difficult
to detect; serious epidemics may occur
Mesoendemic malaria Seasonal or periodic
following good rains
11–50, depending
on survey
timing
Mosquito populations fluctuate, detectable
seasonally; seasonal outbreaks occur; some
detectable immunity in the population
Hyperendemic malaria Intense transmission
(seasonal) each year
51–75 Seasonal fluctuation in malaria cases; severe
sequelae frequent in young children; some
immunity in adults
Holoendemic malaria Transmission may occur
throughout the year with
periods of high
transmission
⬎75 Mosquitoes detectable throughout the year
although with seasonal peaks; high levels of
anemia in very young children; immunity
seen in adults
a
Rate in children aged 5 to 10 years.
282 SHIFF CLIN.MICROBIOL.REV.
the peripheral clinics. Training is minimal and could also in-
volve local commercial outlets for antimalaria drugs. It is an
effective stopgap strategy to cope with epidemics of malaria
when emergency situations arise (125). In crisis situations such
as severe flooding or epidemic outbreaks, it is the strategy of
choice because the tools can be mustered simply and quickly.
The main problem is that chemotherapy alone is not a means
of controlling malaria and is not sustainable in the long term.
There are good data to indicate that treatments obtained from
unskilled sources are frequently inappropriate and often inef-
fective and may promote drug resistance in the parasite pop-
ulation (18, 35, 76). The first-line drugs in current use, chlo-
roquine and pyrimethamine-sulfadoxine, are becoming less
effective due to increasing resistance. Replacement drugs are
costly and may not be acceptable for use in understaffed clinics.
Effective diagnosis would help with this problem. However,
despite the availability of rapid diagnostics that are readily
interpreted by unskilled clinic workers (71, 91), little effort is
made to introduce them into widespread use. Persistence with
chemotherapy alone will buy time but will create very serious
problems in the future.
This global strategy was endorsed by the technical expertise
present to advise Ministers at the Amsterdam Conference, but
it was not without its critics. The Hon Timothy Stamps, Min-
ister of Health for Zimbabwe, noted “If one considers the final
tables in the Global Strategy, one can only presume these to be
sterile impractical assumptions of a disintegrating scientific
technology. No significant guidance was offered for countries
like Zimbabwe which needs to protect her precious human
resources.” As a result of the adoption of the Global Strategy,
the Zimbabwe Ministry of Finance refused to continue with
the old programs and reduced annual expenditure on malaria
control from 3 million to 0.8 million U.S. dollars (106). Such
concerns are currently expressed, perhaps with greater discre-
tion but nevertheless with the same urgency, by Baird (12).
Transmission control. The transmission control strategy rec-
ognizes that malaria is an important cause of morbidity as well
as mortality. The disease is extremely debilitating and extracts
a high price from the communities affected. Children are ane-
mic and unable to concentrate at school (90, 98), and society as
a whole is debilitated. Whereas appropriate treatment is one
aspect of the transmission control strategy, vector control is
also a major player, and, properly applied, these aspects to-
gether have an impact on both the mortality and morbidity of
malaria. This approach is effective in most epidemiological
conditions (Table 3) and is an effective control strategy for a
sustained attack on the malaria problem. It is adaptable to the
use of insecticide-treated mosquito nets as well as indoor
spraying of insecticide (26, 30, 50). It can be implemented in
specific circumstances where malaria is a local priority or on a
wide scale as part of a major program of intervention. Trans-
mission control requires coordination and the development of
strategic plans to intervene against malaria (50). A high level of
expertise is needed with personnel trained in epidemiology and
vector control as well as in planning, mapping, and communi-
cations to coordinate and supervise the operations. However,
these would be the prerequisites in countries which have made
commitments to controlling malaria.
Concerns have been raised by some health authorities (24,
66) that transmission control will eventually reduce local im-
munity acquired from longstanding infection in the population.
This is true. Effective transmission control will reduce the
incidence of infection and reinfection in the community, and
eventually people will lose their acquired immunity. Therefore,
such interventions should be planned in a sustainable manner.
It is incumbent on the local government to recognize this when
making commitments to malaria control. However, the tech-
nique can be incorporated into national malaria control
schemes on a stage-structured basis in areas of high priority. It
is even possible to create barriers to seasonal encroachment of
vector populations and the potential for transmission to invade
populated areas or towns (51).
Eradication of malaria. Eradication can be considered only
in certain areas, e.g., in places where malaria has been eradi-
cated and where it has been reintroduced and in areas of
hypoendemic malaria where there are sufficient resources to
undertake the process and where there is little likelihood of
future introduction. The advantage of an eradication program
is that it is time limited and, once it has achieved its objective,
can be terminated with little further oversight (119). In Table
1 the relative successes of the various malaria control activities
commenced in the mid-20th century period are outlined.
Clearly, eradication programs were extremely successful, but
eradication could not be achieved in many places and the
technique must be considered not appropriate in most areas of
endemic infection.
TOOLS TO CARRY OUT MALARIA CONTROL
Personnel and Strategy Development
Malaria control is a scientific, technical activity that requires
skilled and dedicated staff with training in epidemiology, en-
tomology, mapping and planning, and manpower manage-
ment. Since much work is in the field, it requires personnel
prepared to undertake field work. This is not an arena for pure
clinicians or laboratory scientists, and although all play a role
in the fight against malaria, the control operations are the
realm of malariologists (45). The most important tools to con-
trol malaria consist of properly trained personnel with author-
ity to coordinate and carry out their scientific work (94).
The rest of the tools to control malaria are still fundamen-
tally similar to those used for eradication and control pro-
grams, i.e., the use of insecticides directed against adult mos-
quitoes to reduce the pressure of transmission in the human
population and effective treatment to cure cases as they are
diagnosed. In spite of years of research, there are no new
techniques; in fact, with the advent of drug-resistant P. falci-
parum, we now have a less effective battery of drugs which can
be applied safely in community-wide programs (37, 48).
What has been learned over the past several decades is that
specific control strategies should be developed for specific
country conditions and that there is not a “one set fits all”
method available. We now understand the ecological condi-
tions which affect and regulate the distribution and abundance
of mosquito populations (41). Essentially, efforts to control
malaria must be sustainable and rely on the double-pronged
attack while the sustainability of programs will depend greatly
on the local resources available and should not depend only on
donor support. The extent of a sustainable control program
VOL. 15, 2002 INTEGRATED APPROACH TO MALARIA CONTROL 283
will, of necessity, depend mainly on local resources, which will
then dictate local priorities. The simplest approach, therefore,
is to rely on widespread chemotherapy in populations at risk.
However, wherever possible (and even in areas of restricted
priority) this should be combined with vector control (96). The
use of vector control is not an ancillary factor that can be
conveniently disregarded. It is essential not only to reduce
transmission but also to prevent the development of drug re-
sistance within the parasite population (76). There are good
examples from Zimbabwe of the synergistic effects of the two
methods where integrated malaria control has been in effect in
selected areas for over 50 years (111; K. Day, personal com-
munication). In a recent nationwide survey, chloroquine resis-
tance has been found to occur with any frequency in only three
districts in spite of its use as the first-line drug for all that time
and in spite of the advent of widespread chloroquine-resistant
P. falciparum parasites in surrounding countries, e.g., Zambia
(16, 69, 76). Additionally, combined vector control and pro-
phylaxis using Deltaprim (pyramethine-dapsone) has been un-
der way on a large sugar estate covering a resident population
of 50,000 persons for over 40 years. The local Chief Medical
Officer indicates that there is no transmission of malaria or
breakthrough in prophylaxis on the estate, whereas transmis-
sion does occur in adjacent areas (A. Morar, 2001, personal
communication).
Environmental Management
In a variety of texts, environmental management is proposed
to reduce the number of breeding sites and overall populations
of vector species (93, 96, 122). As mentioned above, there have
been some situations where source reduction was effective
(85). However, on the whole, anopheline mosquitoes are op-
portunistic breeders that favor open sunlit pools or small
streams and rivulets (Table 4). In most cases it is impractical to
suggest source reduction as an effective control effort for
anophelines. Since anophelines are opportunists, their popu-
lations expand during rainy spells and they breed in such a
variety of situations that any attempts to limit the extent of
suitable habitat will not be very successful. Importantly, it is
not the number of mosquitoes that is critical in the cycle but,
rather, the length of mosquito survival which contributes to the
efficient transmission of malaria (40, 60).
Controlling mosquito breeding sites by using spreading oils
or by source reduction is often promoted by health authorities
as a means of limiting nuisance mosquitoes. This is commend-
able since the pests are a considerable irritant to the human
population as well as to domestic animals; however, most peri-
domestic breeding mosquitoes are culicines, which are not
involved in the transmission of human malaria. However, un-
der certain conditions, e.g., in India, where important vectors
(A. culicifacies and A. stephensi) are swamp or pool dwellers,
drainage, the use of larvivorous fish (guppies), or even intro-
duction of polystyrene beads into some habitats may effectively
reduce some populations of mosquitoes by reducing the sur-
vival of larvae and pupae (97). However, the reduction is tem-
porary if not properly managed, and even in India this strategy
does not control an alternative vector, A. fluviatalis; hence, it
has only limited effect on malaria transmission (108).
Any program to control malaria must be tailored to the
species of vectors which are involved in transmission. Antima-
laria interventions should be implemented in a coordinated
manner by an authority which has the technical support and
political power to carry out the programs. In several countries,
particularly in Africa, numerous projects are operated through
a number of agencies which are uncoordinated and which may
have a variety of agendas. Each might provide some local
effect, but none will be sustainable without a national program
which is developed to meet the goals of the local people (gov-
ernment) and which will be sustained and supervised by gov-
ernmental agencies. Sporadic, uncoordinated short-term inter-
ventions are not part of a goal-orientated integrated malaria
control intervention. Even the Global Strategy acknowledges
the coordinating role of government (123). This is necessary to
set priorities which will benefit the nation and help develop a
strategy and to fund and implement the control program (124).
Intradomicile Application of Residual Insecticides
Intradomicile application of residual insecticides, also referred
to as indoor spraying, has been the mainstay of malaria control
operations since the early parts of the last century. Because the
rationale for this method is based on the feeding and resting
habits of most malaria vectors, it is important first to understand
these characteristics of the species of concern. While crepuscular
(twilight) feeding patterns have been noted in a few instances, the
majority of important vectors feed late at night, with peak biting
activities between the hours of 20:00 and 05:00 nightly (117).
Although some species prefer to feed outdoors, endophagy (in-
door feeding) is most common (78, 117).
TABLE 4. Larval breeding sites of Anopheles spp.
Type of habitat Characteristics
Permanent or semipermanent standing freshwater ......................Large open marshes or marshy margins to lakes and ponds
Small ponds, pools or borrow-pits; spring-fed pools and seepages
Standing water in fields, rice fields, open wells, forest pools or swamps
Transient freshwater collections......................................................Open pools in fields, stagnant water in streambeds and cattle hoof-prints, pools
in car tracks and road ruts
Permanent or semi-permanent running freshwater......................Open streambeds with vegetation or running over gravel
Flowing water in canals and ditches, streams in forests and plantations
Brackish water ...................................................................................Marshes, ponds and swamps (not tidal), ponds near salt pans and vleis (dambo)
Tidal swamps
Container habitats (seldom used by anophelines)........................Rock holes, tree holes, plant axils and epiphytic water-bearing plants
Discarded containers (natural and artificial), tins, and tires
Crab holes and cracks in drying mud; water cisterns
284 SHIFF C
LIN.MICROBIOL.REV.
Application. The proper application of insecticide is not
trivial and, if incorrectly carried out, may be quite ineffective.
Although applications can be done by unskilled personnel, a
high level of supervision is necessary (50, 96). The work is
difficult and usually involves hot and sometimes cramped con-
ditions; people tire easily and need encouragement. Addition-
ally, inefficient spraying and even misuse of the insecticide
could occur if supervision is lacking or conniving. To prevent
or control this, it is necessary for rigorous inspection to be
carried out frequently.
Since spray operations are critical in regulating the actual
treatment of the walls and eaves and around immovable fur-
niture, a period of training is necessary (96). Wettable powder
formulations cause abrasion of the spray nozzles, and so these
need to be inspected regularly to ensure correct application of
the spray (118). Ideally, spray solutions should be made up at
a concentration which will treat a specific number of rooms
(Table 5). Before application of insecticide, all furniture, hang-
ing clothing, cooking utensils, food, and other items should be
removed from the house and left covered outside. Indoor
spraying is a very intrusive operation. Strangers are admitted
into one’s private space, which is often a major problem to the
homeowner. It also involves heavy lifting to remove items of
furniture and personal effects prior to the spraying. If there are
no real perceived benefits such as destruction of pests or nui-
sance insects, people soon object to the work, and so it is
important to ensure an ongoing public-relations effort to ex-
plain procedures and motivate the community.
Selection of insecticides. A variety of insecticides are cur-
rently available, and the most appropriate for specific condi-
tions must involve careful study by entomologists (Table 5) and
support of local opinion. For example, the use of DDT or
similar wettable powder may introduce transport costs, since
the formulation is heavy and difficult to transport by bicycle. In
the past, organophosphate insecticides such as malathion (Ta-
ble 5) were substituted for the organochlorines DDT and BHC
(118, 128). However, the cost and increased household disrup-
tion involved with the repeated applications needed for effec-
tive mosquito control have made these compounds unpopular.
If these insecticides are replaced by Deltamethrin or Icon,
much less material is required and a daily supply can be easily
transported by bicycle (5, 110). Other features such as odor
and wall staining are important and must be reviewed with the
community. Finally, there is the element of cost; however,
decisions about supply and expense are usually the subject of
commercial tenders, and final selection is often done by inde-
pendent sources.
Planning. Planning indoor spraying operations requires con-
siderable effort on the part of the health authorities and in-
volves careful mapping of all houses, location of the roads and
routes of access, and generation of the daily work allocation to
ensure that the community is appropriately warned before the
arrival of the spray teams etc. There should be means for
identification of houses so that the records of the spray teams
can be checked on the ground. All the logistics, supplies, and
transport needs must be delineated and budgeted so that the
teams and supervisors all know their duties, allowing the daily
schedule to be properly carried out (50, 111).
Insecticide-Treated Mosquito Nets
The development of synthetic pyrethroid insecticides which
are stable and remain effective for long periods enabled ento-
mologists to test the idea of impregnating mosquito nets of
various textures and fabrics as a vehicle for residual insecticide.
Much has been written about this technique, which is now well
understood and has proven effective (26, 29, 52, 54) (Table 6).
The initial seminal research was carried out in a series of huts
in Tanzania (52). The well-designed experiments of Lines et al.
answered several important questions before the rationale for
the use of insecticide-treated mosquito nets (ITNs) could be
established (56). In a series of trials with volunteers sleeping
either under treated nets or under or adjacent to a treated net
or in huts with no nets at all, the effects on the viability of
exiting mosquitoes was discerned through the use of window
and eave exit traps. Nets treated with permethrin were used for
this work, and the excito-repellency of this insecticide was
discernible in the results. Blood-fed mosquitoes were found in
exit traps, but there was higher mortality among mosquitoes
exiting rooms with treated nets than among mosquitoes exiting
rooms where no treatment was used. This effect was seen with
nets of various dimensions, nets with holes, or torn nets and
even when nets were improperly tucked in or when people
slept on wood frames without mattresses (56).
It is important to return to the basic concept of transmission
control, i.e., reduction of vector life span. Conceptually, the
TABLE 5. Comparison of six insecticides used for house spraying
a
(WHOPES-approved products)
Feature
Organochlorine
(DDT 75% WP)
Organophosphates Carbamates Pyrethroids
Malathion
50% WP
Fenitrothion
40% WP
Baygon 75%
WP (propoxur)
Ficam 80% WP
(bendiocarb)
K-othrine 2.5%
(deltamethrin)
Icon 10% WP
(-cyhalothrin)
Application rate (g of ai/m
2
)
c
2 2 1 2 0.4 0.025 0.025
Residual efficacy duration (mo) 6–12 2–342–32–36–12 6–12
Cost (US$)/kg (product) 3 7 8 20 80 40 75
Cost (US$)/house (200 m
2
) 1.6 5.6 4 10.5 8 8 3.75
Operational cost ratio
b
1.1 5.6 2.5 7 1 2 0.23
Stains walls? Yes Yes Yes Yes No No No
Controls other pests? No Some Some Yes Yes Yes Yes
Odor? No Yes Yes Yes No No No
Refusals? Yes Yes Yes Yes No No No
a
Adapted from reference 118 with permission of the publisher. These insecticides are WHOPES-approved products.
b
The operational cost ratio is defined as the cost per house/freight-saving factor and is given in U.S. dollars for 1996.
c
ai, active ingredient.
VOL. 15, 2002 INTEGRATED APPROACH TO MALARIA CONTROL 285
nets serve as a vehicle for the insecticide. Any ingressing mos-
quito must probe the protecting surface until either it is re-
pelled or finds a hole to enter. This may happen with a treated
net, and the mosquito can take a blood meal. When satiated,
the insect must then probe again, trying to find an exit. During
the process it will acquire a dose of insecticide. This may not be
immediately lethal, but over several feeding excursions the
insect will probably acquire sufficient insecticide to die and
thus not transmit the infection (40).
The use of ITNs is a new and somewhat revolutionary tool for
effective vector control. There is very little infringement on per-
sonal privacy, and the application of insecticide does not involve
seasonal upheaval of furniture, clothing, etc. The method even
provides effective protection from a major source of nuisance,
that of nightly disturbance by mosquitoes (102), as well as de-
stroying bed bugs and other pests (114). However, it is necessary
to note that untreated or improperly treated nets alone do not
provide effective protection from mosquito bites, and touting
them as a means of personal protection may be misleading. Mos-
quitoes can feed through the net when body parts touch the
netting, and access through small holes is well known.
Although ITNs are effective (52), there has to be extensive
coverage and use of nets to achieve a substantial reduction in
malaria transmission, in the same way that this needed for
indoor spraying to be effective (17, 30). In a Tanzanian project,
household coverage approached 75%, and contributed to a
reduction in slide positivity (relative risk, 0.45) and febrile
episodes (relative risk, 0.38) and improved weight gain in chil-
dren younger than 5 years who slept under treated nets (90,
98). There was also a major impact on the density of infected
mosquitoes in the protected areas (99, 113). There is little
doubt about the efficacy of the system in reducing both child
mortality and morbidity (3, 82). The use of ITNs could be
integrated into any national malaria control strategy. Depend-
ing on the behavior patterns of the local vector species, ITNs
could replace indoor spraying in many instances (74). The
main problem to be addressed is the process of implementing
and sustaining operations which are dependent on community
support. Whereas indoor spraying can be carried out by gov-
ernment edict in a centrally planned, vertical-type program,
ITNs can be introduced only in a systematic manner via a
well-informed and committed community. Public information
is a necessity and must be seen as an ongoing activity.
TECHNIQUES FOR IMPLEMENTATION
OF ITN PROGRAMS
Finance and Subsidy
Any discussion about financing public health programs
raises the important issue of subsidy, particularly when one
section of society bears the impact. To what extent can the
overall cost be shared? In developed countries, impoverished
communities are seldom expected to bear the entire brunt of a
public health intervention which in the long run will benefit the
nation as a whole. This reviewer asks, should not those com-
munities embracing malaria control activities for both personal
and public good be entitled to some subsidy to defray their
individual costs? One proceeds with an assumption of a re-
sponse in the affirmative, even in light of certain agencies
requiring full cost recovery. While such cost recovery may
appease many economists, this is not the basis of public health.
There are several approaches for financing the distribution
of ITNs as a means of vector control, ranging from outright
gifts to sale of the items at commercial or subsidized prices. In
the first situation, there is the hope that recipients will respect
the items and use them for the purpose of malaria control.
Alternatively, agencies are encouraging the sale of treated nets
as a commercial activity promoted by advertising, together with
some health education and some form of cost recovery (9). It
is now accepted that the concept of sale and private ownership
of mosquito nets is likely to be acceptable and result in their
general use (9, 65, 105). Current information indicates that
with the more active pyrethroids, e.g., deltamethrin, annual
treatment will be sufficient (28). Merely handing out the nets
does not mean they will be used, and there is considerable risk
that many of the free nets will be sold on the open market by
the recipients rather than used for protection against malaria.
More importantly, if they are part of an overall strategy for
malaria control, then the system will not achieve its overall
TABLE 6. Implementation of malaria control by using ITNs
Activity Critical implementation conditions Implementation process
Strategy Concept should be incorporated in a national malaria
control program based on vector control
Nets and insecticide sold or distributed
to target communities
Promotion (type 1) Education to inform and convince population; supervision
and coordination by community leaders (or malaria
action committee)
Community involvement
Promotion (type 2) Role for trained technical support staff; overall supervision
and monitoring of all implementation activities
Strong, motivated support scientists;
need overall authority for
coordination and control
Affordability Public are asked to bear some costs; need for marketing of
commodities and subsidy to purchasers; arrangements
for assisting impoverished persons
Honest and transparent financial
transactions under coordinating
authority
Insecticide use Proper treatment and reimpregnation of nets is essential;
education of target communities, careful supervision,
and motivation needed
Supervision and control by dedicated
technical personnel
Evaluation Trained epidemiologists, entomologists, and support staff
must be employed by malaria control authority
Deployment of trained staff to collect
data; adequate facilities including
transport; computerized support
286 SHIFF C
LIN.MICROBIOL.REV.
objective. With personal ownership in mind, there are two
main approaches to consider.
The first is the sale of subsidized ITNs, with the proceeds or
profits being converted into a community-held revolving fund
that pays for sustaining community participation, purchase,
and distribution of replacement nets as needed (79). If nets
retail at approximately 75% of the street price, people are not
inclined to sell or otherwise dispose of them (9, 102). These
nets and additional insecticide can be obtained with some
subsidy through the commercial sector, and the whole enter-
prise would be overseen by trained research and control offic-
ers who are retained by the Ministry of Health. Such a system
was developed by the Bagamoyo Bednet Project (65).
The second is the promotion and sale of necessary items
through a process of “social marketing” within the community.
The nets and insecticide are packaged attractively and made
available for sale through commercial outlets, although the
promotional activities and some of the distribution costs are
underwritten via large donor agencies (62, 105). A large
project under the name KINET has reported success in south-
ern Tanzania but with subsidies of 33 and 83% for the nets and
insecticide, respectively (9). Reports available on these activi-
ties usually focus on the success of sales but omit anything
about reimpregnation activities (105).
These systems both require an input of external financial
support because the full commercial cost of both nets and
insecticide will preclude ownership and use by large sections of
the public. If ownership of ITNs is limited to those who can
afford them or to a small section of the community such as
pregnant women, these individuals may get some personal
protection but the efforts will not contribute to malaria control
and could not be considered an effective element of a public
health intervention against malaria.
Reimpregnation
A key element in the ITN program is the need for nets to be
retreated regularly with insecticide. Without reimpregnation,
the nets will lose their function as vector control agents (Table
6). It is essential that concerted efforts be made to ensure that
people understand that the nets must be retreated regularly
(annually) and that they should bring the nets to a center to
have this done (or treat the nets themselves) (72, 73, 102). This
task requires effort on behalf of the community and the super-
visory staff. Also, logistics concerned with procurement, distri-
bution, and use of insecticides must be put in place. Misuse of
the insecticides must be scrutinized to ensure proper retreat-
ment activities, and cash flow must be transparent and properly
managed. In rural areas where community participation is an
integral part of the program, financial remuneration for the
workers may be necessary; this can best be done with a revolv-
ing fund where the interest accruing may be used for payment
of services rendered by the committee (65, 102).
The issue of regular retreatment of nets has been the subject
of much research and debate (9, 27, 29, 75). It is now consid-
ered that ITNs operate with similar efficiency to indoor spray-
ing programs but with certain advantages (Table 6). Industry
has developed single-dose tablets of deltamethrin (KO-Tabs)
for individual use, but these packages are more expensive than
group treatments. Large-scale treatments usually cost about 20
to 30 cents (U.S. currency) per net for the insecticide. Re-
cently, nets produced under the name Permanet and treated
with a propriety formulation of deltamethrin have been
claimed to remain insecticidal for up to 4 years. Curtis (C. F.
Curtis, abstract from the Vector Control Workshop hosted by
the London School of Hygiene and Tropical Medicine in Sep-
tember 2001, abstr. 2.2, 2001) has tested these pretreated poly-
ester nets, but there has not been sufficient time to determine
the duration of insecticidal efficacy. In comparative trials, the
knockdown time for bioassay with mosquitoes (300 s) was
similar for both Permanet and normal nets treated with the
same dose of deltamethrin; even after 20 successive launder-
ings, the knockdown time was similar (600 s), and data suggest
that the Permanet polyester nets were more wash resistant
than conventional nets treated with deltamethrin (28). This
information does not disprove the efficacy claims of Permanet,
but this is an area of critical research.
Sustaining the Intervention
Interested and motivated communities are important to sus-
tain an intervention. For this to be effective, people should
know what is expected of them and what they will receive in
return. There should be a clear statement of activities, respon-
sibilities, and rates of remuneration for people who provide
time to do the work (65). This can be done if the scopes of
work are defined and codified in a “constitution” that is agreed
upon collectively. This was done in Bagamoyo, and the final
document approved by the various communities contained de-
tails of membership, specifying the membership composition
(i.e., the number of women, teachers, and medical personnel)
and means of election. Each job category, the activities in-
volved, the number of formal meetings to be held, their fre-
quency, and the specific activities which were to be reviewed
were described (65). To maintain a consistent level of remu-
neration, the interest accruing from the revolving fund was to
be distributed among the personnel according to the number
of hours worked and individual achievements. This work pro-
gram was to be reviewed by a medical official, e.g., the malaria
officer, a member of the local Ministry of Health staff. Money
could be removed from the fund established in the Bagamoyo
district only with a cheque bearing three signatures, two from
the committee and one from the malaria officer, thus ensuring
that funds were, for the most part, used appropriately.
The alternative method proposed for sustaining interven-
tions, that of social marketing, while popular with donor agen-
cies, has also raised queries (9, 105). Despite considerable
public relations work and initial advertising, there is no evi-
dence as yet that it will be effective in controlling malaria in any
national program or that the system will be sustained without
continual financial input from the donors.
STRATEGIES BASED ON BIOLOGICAL
CHARACTERISTICS OF MALARIA TRANSMISSION
Barrier Spraying
Under certain conditions, particularly when there are strong
seasonal fluctuations in vector mosquito populations and the
species survive the winter by seeking refuge in warmer, humid
VOL. 15, 2002 INTEGRATED APPROACH TO MALARIA CONTROL 287
areas, barriers to mosquito invasion can be created by limited
but intense vector control operations. Properly designed, these
will help prevent the periodic invasions of areas of hypoen-
demic infection or areas vulnerable to severe epidemics. Such
areas are usually in proximity to regions where transmission is
more stable or even permanent. Designing systematic control
operations in the areas prone to invasion can prevent the
migration of mosquitoes into vulnerable areas, thus reducing
the threat of serious epidemics in highly populated areas. Ar-
eas of hypoendemic infection are usually cooler (or drier) than
areas of mesoendemic infection and therefore may be densely
populated or may be of considerable economic importance.
Outbreaks in populated areas can have catastrophic effects on
public health and the economy of the country where infection
is endemic. The use of barrier spraying programs to prevent
the movement of vector mosquitoes from their dry season or
winter refuges can be effective in curtailing the spread of ma-
laria into vulnerable areas. However, to be effective, barrier
spraying requires detailed knowledge of the mosquito popula-
tions, their winter refuges, and the seasonal conditions which
allow their spread into adjacent areas.
An example used in Zimbabwe was based on Leeson’s obser-
vations that A. gambiae sensu lato and A. funestus found winter
refuges in the northeast of that country (51) (Fig. 1). In the spring,
as conditions warmed in the areas above 900 m, vector species
began to invade the upland areas and could be collected in pools
along river valleys, progressively moving into more temperate
areas. From these refuges, malaria spread into the adjacent farm-
ing and urban areas with devastating effects. A concerted system
of intradomicilary spraying across these lines of invasion just prior
to the seasonal warming period served to protect invasions of
high-density population areas, which were of economic impor-
tance to the country (5, 6). The importance of altitude and tem-
perature in the seasonal ebb and flow of malaria under hypo- and
mesoendemic conditions was stressed by Taylor and Mutambu
(111). These data support the successful malaria control opera-
tions which guided the Ministry of Health in Zimbabwe for over
50 years and which have only recently been inadvertently disman-
tled. This dismantling is a result of the drive to decentralization
required by international donors and has contributed to recent
increases in transmission (1.8 million cases of clinical malaria
recorded in 1998) (8).
The concept of barrier spraying can be applied in numerous
epidemiological situations, provided that there is sufficient ex-
FIG. 1. Map of Zimbabwe showing regions of malaria endemicity. The regions of differing malaria endemicity are shown in color. The red area,
mainly below the 600-m contour except in the elevated mountain ranges, is holoendemic; the orange areas, also around the same elevation, are
more seasonal and dependent on rainfall; in the green areas, transmission is unstable and seasonal; transmission in the yellow areas, above the
1,200-m contour, is hypoendemic or nonexistent. The districts between 900 and 1200 m (green) represent the area routinely sprayed in the past
antimalaria program. In these areas, both vector control and chemotherapy were undertaken. In other areas, the Ministry of Health relied on
chemotherapy alone that was provided through the rural clinic services to prevent outbreaks of malaria. The green zone acted as a barrier to
prevent the encroachment of malaria onto the high plateau, which was the most heavily populated part of the country.
288 SHIFF C
LIN.MICROBIOL.REV.
pertise to plan and execute the operations. Such methods
could be implemented wherever there is a concern about sea-
sonal encroachment into areas which are considered to be a
high priority by local health authorities and politicians.
Structured Malaria Control
Situations occur where health authorities must attempt to
protect defined communities from epidemics or reduce the
overall intensity of malaria transmission. Under such circum-
stances, the area and community affected would be identified
through specific local health priorities and may expand over
wide stretches of country; however, the extent of the work
would be limited by the availability of a sustained flow of
financial resources. Examples would be large agricultural or
industrial complexes, mines, and even cities or large popula-
tion centers (115), as well as major areas which fall into the
malaria control strategy of the country where the infection is
endemic. In such instances it is feasible to design and plan
interventions based on sustained vector control operations.
These would commence just before the start of the main trans-
mission seasons and would have to be maintained in a high
state of coverage for the duration of the transmission period.
Such interventions require coordination and planning as
well as the cooperation of the local communities involved.
Because the programs involve and protect the overall commu-
nity and even other population groups living in adjacent areas,
it is important that all sectors of the community are kept
informed and participate wherever possible. It is quite feasible
for communities to select the type of vector control interven-
tion which they feel is the most suitable, because in the long
run, sustained success will depend on local interest and effort.
Here again, levels of subsidy and remuneration must be nego-
tiated, because it is essential that high levels of compliance are
achieved in the vector control activities.
This structured approach would incorporate both vector
control and chemotherapy. It would be feasible for the com-
munity to be protected with prophylaxis if the level of organi-
zation can cope with the logistics. In instances where effective
vector control is in place, there should be little likelihood of
breakthrough of resistant parasites. As mentioned above, the
combination drug Deltaprim (pyrimethamine-dapsone) has
been used in such circumstances in southeastern Zimbabwe for
over 40 years with no discernible side effects and little evidence
of failure in a community of approximately 50,000 persons (A.
Morar, personal communication).
Evaluation of Efficacy
There is no need to review past results of the use of indoor
spraying to control transmission of malaria; its efficacy is well
known and accepted (47). However, the effect of ITNs remains
a matter of debate, mainly because there has not been a major
sustained national program in operation outside China (59)
and because in the areas of holoendemic infection where most
trials have been carried out, these trials have been of short
duration, lasting at the most 5 years. However, the indications
are good, and one can expect that sustained ITN programs will
be successful. Original trials in The Gambia (32) and Tanzania
(64) showed a decline in the number of infective mosquitoes
and an improvement in indicators of both malaria infection
and morbidity in the control area. Similar reports have come
from elsewhere in Africa (68, 82, 89, 99) and from other
sources quoted in Net Gain (52). It has been noted that ITNs
may not reduce the overall population of mosquitoes; crepus-
cular (twilight-loving) forms and many culicine species are not
always reduced in number (74). Even specimens of vector
mosquitoes are still found in experimental traps, but since few
of these are actually infected, the effect achieved is to reduce
transmission (68, 113). An ITN program which will reduce the
life expectancy of vector mosquitoes will thus achieve the effect
predicted by the vectorial capacity model.
INSECTICIDES, INSECTICIDE RESISTANCE,
AND MALARIA CONTROL
A list of some commonly used insecticides, together with
cost-effective ratios, is given in Table 5. Although not exhaus-
tive, it does cover the various classes of insecticides in use and
enables comparisons to be made. Unfortunately, mention of
DDT is contentious these days, and therefore some comments
are appropriate. The advent of DDT and other chlorinated
hydrocarbon insecticides provided the mainstay of malaria
control after World War II. In fact, DDT was initially devel-
oped as a public health insecticide prior to its widespread use
in agriculture and its identification as a major environmental
pollutant (25). In spite of widespread use and exposure of
humans across the globe, this insecticide has been relatively
safe for use in public health programs as long as it is not spread
into the environment. When used for indoor spraying, envi-
ronmental contamination is greatly restricted, thus avoiding
entry of the pesticide into the global food chain (10).
Resistance is also important. Widespread use of any insec-
ticide will probably lead to the selection of resistant forms of
the target organism. This has happened in several countries
and with several vector species. However, in spite of its pro-
longed use over nearly 50 years, DDT is still effective in many
parts of the world. Being a cost-effective insecticide for indoor
spraying, DDT still plays an important role in some malaria
control programs. More recently introduced (although devel-
oped for agriculture) pyrethroid insecticides have been ex-
tremely valuable in public health use. In spite of the wide-
spread agricultural usage, Curtis (28) has reported little or no
evidence of pyrethroid resistance among the important vectors
in eastern Africa. In South Africa however, workers have dem-
onstrated significant resistance of A. funestus to pyrethroids
and have recommended reintroduction of DDT spraying in
KwaZulu/Natal (46). In a recent symposium held under the
auspices of the American Association for the Advancement of
Science, the case was made not to ban DDT as a noxious
pollutant because of its importance at a public health pesticide
(94). Considerable debate has taken place about the role of
DDT in public health. The reader is referred to a detailed
summary of a recent discussion by Taverne (109). Properly
used, the insecticide is applied in small quantities to indoor
walls. As such, it is unlikely to contribute to the outdoor pol-
lution problem, and it can help save many lives in the less
advantaged, malaria-endemic regions of the world. However,
indoor application of insecticides may impact the vector pop-
ulation in unexpected ways. In a recent review of malaria,
VOL. 15, 2002 INTEGRATED APPROACH TO MALARIA CONTROL 289
Phillips (89) quotes workers from Brazil who mention changes
in the behavior of A. darlingi, which, although previously en-
dophilic (indoor resting), now moves outdoor soon after feed-
ing and thus is less exposed to insecticide than earlier in the
control operations. Similarly, in Africa, indoor spraying has
eliminated the endophilic A. gambiae in some areas, only to
have it replaced by the more exophilic A. arabiensis (46). How-
ever, transmission by the latter species can still be controlled by
indoor spraying of insecticide (47).
DIAGNOSIS OF INFECTION
As with all infections, rapid diagnosis must be integral to an
appropriate treatment program. However, diagnosis of malar-
ial infection is, for all practical purposes, the purview of village
health workers, trained or untrained nurses, and some medical
officers. Ideally, it should be done in a timely manner by
trained medical laboratory technologists, but even then ma-
laria parasites are difficult to see. This is often exacerbated
when staining conditions are not optimal, a situation which
often happens in rural settings. Even under hospital conditions
where staff are usually under severe pressure, it is difficult to
obtain results in a timely fashion; hence, most diagnoses in
regions of endemic infection are based on clinical symptoms.
When the patient is nonimmune, clinical indications are usu-
ally suggestive of malaria, but in areas of endemic infection
these are extremely misleading and fraught with inaccuracies.
Studies in northeastern Zimbabwe of 104,000 cases over a
12-month period showed that fewer than 30% of diagnoses
made by trained nursing staff operating at rural clinics were
slide positive (P. Taylor and A. Taputaira, Zimbabwe Sci. As-
soc. First Natl. Symp. Sci. Technol., 1988). A similar result was
noted in Madagascar, where only 12% of 6,884 presumptive
diagnoses carried out in hospitals between 1997 and 1998 were
found to be slide positive (2). This discrepancy is not always
seen. In Ghana, malaria diagnosis at a health center was shown
to be 62% slide positive (35). However, this was still three
times more accurate than in home diagnoses (35). Unskilled
home diagnosis is likely to be the most inaccurate means of
diagnosing malaria and will result in high proportions of un-
necessary and inappropriate treatments.
In response to the obvious need for rapid, easily interpreted
diagnostics, a series of rapid malaria tests have been developed
based on detecting parasite-specific circulating antigens such
as HRP-2 (86). The dipstick tests use specific monoclonal
antibodies to detect these antigens and reveal positive reac-
tions with a colored line as in the ParaSIGHT-F test (91, 100).
Over time, new products have been developed which use sim-
ilar monoclonal antibodies. The ICT-Pf/Pv test, which detects
HRP-2 of P. falciparum and also a unique antigen expressed by
P. vivax (49, 92), is thus able to discriminate between these two
parasites. Both these antigen capture tests perform well with
high sensitivity and specificity and have been extremely widely
tested. Since they detect circulating antigen, these assays re-
main positive for about 10 days following treatment (100).
These tests may also cross-react with rheumatoid factor (43),
but that does not reduce their exceptional value for rapid and
effective diagnosis of both important malaria parasites (71). An
additional dipstick test which detects the enzyme lactate dehy-
drogenase and so also recognizes both parasite species has
been tested in Central America (84) and India (104). This test
has the advantage of turning from positive to negative in about
5 days after effective elimination of the parasites. Selection of
the appropriate test is probably most dependent on cost, an
issue which precludes the more widespread use of these im-
portant diagnostic procedures at this time.
Because of the importance of these tests in the overall
Global Strategy of Malaria Control, there should be some
drive to subsidise or reduce costs for the tests in countries
where infection is endemic in order to make them economical
and of greater value in malaria treatment programs. Perhaps
this would be a role for Roll Back Malaria or WHO.
TRAVEL MEDICINE AND PROBLEMS DUE TO GLOBAL
CLIMATE CHANGE
The problem of imported malaria is gaining notoriety in devel-
oped countries. MMWR Reports from CDC (www.cdc.gov) have
shown gradually increasing numbers of cases detected in the
United States, peaking at over 2,000 in 1980, but since then the
case detection rate has remained around 1,600 annually. In the
United States this presents a hazard of initiating so-called cryptic
cases, which are probably mosquito borne. Several good vectors
of malaria exist in the country, A. hermsi in California and A.
quadrimaculatus in the south and much of the east; these species
are capable of picking up gametocytes and initiating foci of trans-
mission (45; MMWR Reports [www.cdc.gov]). Imported malaria is
of increasing concern in Europe (83). In Aberdeen, over a 5-year
period 110 cases of malaria were diagnosed; 60% of patients had
P. falciparum infections, and the remainder were mainly P. vivax
infections. The majority of infections were acquired due to lapse
or absence of prophylaxis (63). A similar casual attitude has been
reported from the United States, where records in San Francisco
over a 10-year period ending in 1997 show that only 23% of
travelers to areas of endemic infection had been compliant with
antimalaria prophylaxis and none of these had developed infec-
tion (34).
Diagnosis of these imported cases is critical because of the
life-threatening condition which may develop from a P. falci-
parum infection. A recent study in Italy comparing genus-
specific PCR and Southern blot species-specific hybridization
with rapid diagnostics and microscopy showed the advantage
of both good-quality microscopy and the rapid diagnostic tests
in securing a rapid and accurate diagnosis. PCR and micros-
copy had 100% agreement, while the rapid ParaSIGHT-F test
showed a specificity and sensitivity of 94% (88).
With the impending changes in global climates, the problem
of imported malaria will become more widespread because of
the spread of malaria into new areas of endemicity and the
cavalier attitude regarding prophylaxis among overseas travel-
ers (63). In areas of endemicity, encroaching transmission has
been reported in areas previously free of transmission. This is
likely to be a response to warming conditions or else to periods
of prolonged summer rains which occur as a result of extreme
climatic episodes, which are becoming more frequent. Exam-
ples of this can be seen with the advent of malaria epidemics in
the highlands of Madagascar (2); Kenya, where transmission
may encroach on Nairobi and the Kenya highlands; and
Uganda, where similar encroachment is happening (55) as well
as in Lusaka, where malaria transmission occurs occasionally
290 SHIFF CLIN.MICROBIOL.REV.
although the city was previously free of transmission (14).
When conditions favor the extension of transmission into these
previously malaria-free zones, increasing numbers of travelers
are likely to return home with prepatent infections.
MALARIA VACCINES
Attempts to develop a malaria vaccine began early in the 20th
century, and in spite of advances in biomedical technology and
periodic bouts of unsubstantiated optimism in the field, no effec-
tive vaccine is available for use (95). It is not the purpose of this
review to cover the current status of malaria vaccine develop-
ment. However, mention of the various strategies pursued by
research workers is in order so that we can develop a perspective
of how vaccines may be utilized in controlling malaria.
The development of malaria vaccines has become the focus of
considerable research. On the basis of research with rodents,
scientists in the early 1970s demonstrated that irradiated sporo-
zoites of P. falciparum and P. vivax inoculated into naive volun-
teers would provide protection against challenge from fully infec-
tive mosquitoes (7, 23). The main opportunity for this work to
flourish occurred following the decisions to reduce emphasis on
eradication programmes in the early 1970s (120). This was a
period when discoveries in molecular techniques were incorpo-
rated into the studies of the malaria parasite. The fact that P.
falciparum was amenable to in vitro cultivation prompted this
species to become the main focus of study, an emphasis which has
lasted until the present. The situation with P. vivax is more diffi-
cult because this species cannot yet be cultured in vitro. With P.
falciparum the research effort has followed three main routes. The
first has been to try and destroy circulating sporozoites before or
during early stages of infection of hepatocytes to produce a sterile
immunity. The second has been directed against the blood stage
antigens of the parasite trophozoites in an attempt to reduce the
virulence of infection and, by preventing further development of
schizonts, to interrupt reproduction. Finally, there is an approach
to prevent the development of sexual forms, and if they do de-
velop, to attack the maturing forms when ingested by the vector
mosquito. This last strategy is called transmission-blocking immu-
nity. Cocktails of these vaccines are being contemplated (95).
Research has brought several candidate vaccines through
phase 1 and in some cases phase 2 of vaccine development.
The only vaccine to reach phase 3 was a multicomponent
synthetic peptide, SPf66, which was claimed to have protective
effects in trials in Columbia (87). The vaccine was tested in a
series of trials in holoendemic situations in Africa (4, 31) and
showed marginal, if any, protection. Finally, no protection was
observed in a trial when it was incorporated in an Extended
Program of Immunization program and administered to chil-
dren as part of the initial immunization program (1).
FINALE: ROLL BACK MALARIA
Malaria control is an increasingly important focus for the
international body concerned with public health and disease
control. The need for reactivation and revitalization of past
control programs, finance to support interventions, and the
need to rationalise the concepts of malaria control has been
seen by senior administrators such as Gro Brundtland, Direc-
tor General of WHO. In response, the Roll Back Malaria
initiative has arisen with backing from the United Nations
Development Program, World Bank, United Nations Chi-
dren’s Fund, and WHO (80). Philanthropic organizations such
as the Gates Foundation, the National Institutes of Health,
and others have added resources to this body, so that the
enterprise has considerable opportunity to make an impact.
The initiative is examining various strategies to do this. How-
ever, to any observing malariologist, the main weakness glo-
bally is the dearth of trained, properly remunerated technical
personnel prepared to work in the field (13).
Without local expertise to develop local strategies for the im-
plementation of control programs, ministries of health will floun-
der in the process of implementation and their efforts will dissi-
pate. The underlying necessity required to develop and sustain
national programmes is to rebuild local infrastructure and exper-
tise. This will require selection and training of local personnel
from countries with endemic infection who have a commitment to
learning about malaria and who will remain and develop their
careers locally. There is a need for the local governments and also
universities to offer such personnel the basic elements for career
development (101, 103). This is the challenge for Roll Back Ma-
laria, to help reestablish scientific civil services in areas of endemic
infection since such organizations are the root of internal stability
and drive. There is no easy solution, but one is essential otherwise
we will have no real program for malaria control, neither this year
nor in 10 years.
ACKNOWLEDGMENTS
Many of the thoughts expressed here are based on nearly 30 years of
experience in malaria control in the country now called Zimbabwe. For
the camaraderie and collaboration over these years, I must express thanks
to members of all the malaria teams with whom I worked.. Particularly, I
thank Vic Clarke, Director of the Blair Research Laboratory, who pro-
vided the inspiration and leadership which made the programs the success
they were. Thanks are due also to Don Roberts of the Uniformed Uni-
versity of the Health Sciences for his suggestions regarding control pro-
grams in Central and South America and to Doug Norris of Johns Hop-
kins for his revisions and suggestions. Finally, my deep thanks go to David
Clyde, a lifelong friend and colleague who has dedicated so much of his
life to malaria control in Africa.
Financial support from the Johns Hopkins Malaria Research Insti-
tute is acknowledged.
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