Trends in antimalarial drug deployment in sub-Saharan Africa
Malaria Epidemiology Branch, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA
* Author for correspondence (e-mail: Pbloland{at}cdc.gov)
Accepted 18 July 2003
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Summary |
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Key words: antimalarial drug resistance, Africa, malaria, drug deployment, treatment effectiveness
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Introduction |
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Achieving effective antimalarial drug deployment over the short- to medium-term will require an appreciation of how drugs are currently used in the real world and development of innovative approaches to optimize that use. Over the long term, however, effectively responding to antimalarial drug resistance will come to a choice between maintaining business as usual (which would include an on-going need for rapidly developing and deploying new malaria treatments in order to keep up with, if not stay ahead of, developing drug resistance) or making fundamental changes in how drugs against malaria are used in practice, in order to sustain their useful life spans as long as possible.
Despite malaria being an illness that claims as many as a million lives each year in Africa, antimalarial drugs are used within an environment that is characterized by a great degree of nonchalance. This nonchalance is largely the result of many years of surprisingly successful use of the most common antimalarial drugs, particularly chloroquine (CQ). In many situations, practices that could best be described as misuse of drugs have become routine, and in some cases, institutionalized and promoted.
Over years of deployment, there was little incentive to improve the way that antimalarial drugs are used. Both CQ and sulfadoxine/pyrimethamine (SP) were inexpensive, making it more cost-effective to treat presumptively rather than to attempt to get microscopic confirmation (especially when this is unavailable, a common situation in Africa). As both drugs were relatively safe, treating uninfected people, including infants and pregnant women, for malaria carried minimal health risk. More importantly, because of the risk of severe or fatal malaria in these groups, the potential for placing the individuals with malaria infection at even greater risk due to delays in obtaining a definitive diagnosis was felt to far outweigh that of providing malaria treatment to the many women and children who were not infected.
As is true with many different drugs in practically all cultures, it is recognized that antimalarial drugs are often taken in incorrect or incomplete doses. For years, CQ was highly efficacious, so incomplete dosing was still likely to reduce the parasite load, if not eliminate it. CQ has an antipyretic effect and can provide some relief of symptoms even if parasites persist. Among patients with sufficiently developed acquired immunity, underdosing of CQ may still be sufficient to prevent progression to severe disease or death in many, if not most, circumstances. In fact, lack of parasite clearance post-treatment was deemed by some experts to be a desirable outcome, based on an unproven assumption that this would be necessary so as not to interfere with the acquisition and maintenance of partial immunity.
For decades, malaria therapy was also relatively easy to give. In Africa,
CQ was initially given as single dose treatment (10 mg kg-1) (WHO,
1973,
1986
). As resistance
developed, the recommended dose increased to 25 mg kg-1 given over
3 days (although the proportion of patients actually taking all three doses
was low) (WHO, 1986
). As CQ
resistance further intensified and spread, some countries switched to SP,
going back to an easy-to-give, single-dose regimen
(Bloland and Ettling,
1999
).
Until recently, therefore, first-line drugs for malaria were inexpensive,
easy to give, safe and, at least initially, highly efficacious. While there
was some concern over adherence, as demonstrated by a few studies looking at
this phenomenon, there was little effort or incentive to devise strategies to
improve the way that CQ or SP were deployed
(McCombie, 1996;
Deming et al., 1989
;
Slutsker et al., 1994
;
Ruebush et al., 1995
). This
indifference has changed only recently.
While most of the newer malaria treatments currently recommended do offer much-improved parasitologic efficacy over failing treatments like CQ and SP, that increased efficacy typically comes at a cost, both an increased economic cost and a cost of increasing complexity. Newer treatments tend to be much more expensive and are more difficult to administer. Furthermore, their safety is relatively unproven, especially among the highest risk groups for malaria in sub-Saharan Africa, young children and pregnant women. In some countries, these newer pharmaceuticals are about to be deployed on a relatively large scale long before the country's medical community has gained any practical experience with them. For the most part, few countries have considered how the introduction of newer treatment regimens might affect the delivery system. While the drug names and dosing schedules may change, the environment in which they are deployed is expected to remain unchanged.
This situation (comparatively high drug cost, complex regimens, uncertain safety, poor diagnosis, heightened concern over resistance) argues strongly in favor of a fundamental change in the way that antimalarial drugs are deployed and used. Such fundamental changes would require a new vision of malaria treatment policy and practice and substantial investments into health infrastructure within both the public and private sectors.
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Paradigms of antimalarial drug deployment |
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The first paradigm opts for sensitivity in case finding over specificity
and maintains that the best approach to reduce malaria morbidity and mortality
is to make effective treatment widely and freely available down to the most
peripheral level, the household. Essentially, anyone with even a small chance
of being infected receives treatment (even in situations where as few as 5% of
febrile patients are actually infected)
(WHO, 1997). This approach is
a fundamental part of the Global Strategy for Malaria Control and Roll Back
Malaria, and is a major component of related strategies, such as the Abuja
Declaration goals, and the Integrated Management of Childhood Illnesses (IMCI)
program. Such an emphasis on deploying efficacious malaria treatment as widely
as possible is supported by observations that, under experimental conditions,
it can reduce severe malaria-related morbidity and overall mortality among
young children (Pagnoni et al.,
1997
; Kidane and Morrow,
2000
).
The alternative paradigm, which favors specificity over sensitivity, maintains that a primary objective of malaria therapy should be to limit the advent and spread of drug resistance. Because drug pressure is a leading contributor to intensification of resistance, this paradigm stresses that access to treatment should be controlled sufficiently to ensure that only those with confirmed diagnosis receive treatment. This approach recognizes, even emphasizes, the existence of a very limited antimalarial armamentarium, and a slow and costly process involved in developing new antimalarial drugs.
The two paradigms are clearly at odds on a number of issues. To date, no data have been systematically collected to examine the impact that widespread, easy access to antimalarial drugs (such as described above) would have on drug resistance or other important health outcomes. Similarly, the desire to limit provision of antimalarial drugs to those who need them fails to account for the systematic realities that limit the availability of accurate diagnosis to only a small fraction of the African population.
Some of the programmatic implications of these approaches on how drugs should be deployed are outlined in Table 1. The way forward for Africa will most likely depend on a rational compromise between these two polar-opposite paradigms. Currently, compromise between these paradigms is occurring, but in an ad hoc, or even accidental, manner rather than through coordinated effort. Achieving durable and programmatically effective implementation of new treatment strategies will require a more purposeful and informed merging of these approaches.
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Programmatic effectiveness: a public health approach to malaria treatment |
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More recently, broader concepts of what it means for a malaria drug to `work' have been introduced, due in large part to the development of epidemiology and public health practice as disciplines in their own right, as well as an increased interest in malaria on the part of anthropologists, economists, and other social scientists. For example, for a drug to `work', it must not only clear parasites, but must also be perceived to have worked on both an individual and cultural level. In some situations, the perception of treatment is more important than its biological effect.
With the input of these additional disciplines, not only have concepts of what it means for a drug to work changed, but also greater emphasis has been placed on understanding why drugs might not work. Greater emphasis on the influence of cultural beliefs, treatment-seeking behavior, household economics, actual behaviors and practices, among others, have all contributed to a more comprehensive concept of antimalarial treatment.
This more inclusive concept of malaria treatment, programmatic effectiveness, is the first that truly addresses the issues that are central to actually achieving reductions in malaria morbidity and mortality. Programmatic effectiveness attempts to identify and maximize the favorable outcomes at the critical junctures that occur between infection of an individual with malaria parasites and ultimate clearance of those parasites and survival of the infected individual. It is through this process of maximization that the most reasonable compromise between the two conflicting paradigms of treatment will occur and, in turn, malaria control programs can achieve the greatest impact that treatment can have on malaria and morbidity.
Two examples of the concept of programmatic effectiveness related to
malaria case management have been published. In the most recent, a Piot model,
previously used successfully to evaluate TB and sexually transmitted infection
control programs, was developed for malaria case management
(Mumba et al., 2003).
According to this model there are six steps that a patient would have to
achieve in order to be successfully cured of malaria: awareness of a need for
treatment, motivation to seek treatment, diagnosis, initiating correct
treatment, completing that treatment, and the treatment being efficacious. The
second example takes a similar approach and applies it to a specific situation
(Krause and Sauerborn, 2000
).
In this model, the authors have identified what they felt were the critical
steps in correct management of malaria: (i) patient seeks care at a health
facility, (ii) a complete history is taken, (iii) a complete physical
examination is performed, (iv) the correct drug at the correct dose is
recommended, (v) the correct drug at the correct dose is bought by patient,
(vi) the complete dose is taken and (vii) the drug is efficacious. Using data
collected in Burkina Faso, the authors suggest that only 3% of patients are
actually managed correctly. Furthermore, both examples illustrate that
optimizing a single factor while leaving the other factors alone can have
minimal impact in terms of improved case management: in the Burkina Faso
example, increasing the efficacy of the antimalarial drug used from 85% to
100% increased overall programmatic effectiveness by <1%. The authors
correctly point out that patients could still achieve a favorable outcome even
if not correctly managed (for example, receiving and taking the correct drug
at the correct dose could occur even though the health care worker did not
take a complete history or perform a proper physical examination), and clearly
the selection of which steps are truly critical for optimal case management is
open to debate. Nonetheless, it is a logical conclusion that morbidity and
mortality will decline as more patients receive correct management, and that
optimizing correct management will require a holistic approach rather than
single-minded focus on isolated factors taken one at a time.
Programmatic effectiveness has implications for more than just patient outcomes. Many of the components of effectiveness that contribute to improved patient health will also contribute to selection for and/or intensification of drug resistance: critical components such as the quality of the drug being used and the ability and willingness of the patient to correctly take a complete treatment will also either facilitate or inhibit drug resistance.
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Trends in antimalarial drug deployment |
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Lack of recognition of populations at risk in drug development and
deployment
In tropical sub-Saharan Africa, the two groups at greatest risk of severe
malaria morbidity and mortality are very young children and pregnant women
(WHO/UNICEF, 2003).
Antimalarial drugs must be both safe and effective for the treatment of
malaria in these high risk groups to be of greatest use. Unfortunately, drug
companies often do not conduct the appropriate research to establish safety in
these groups before marketing their products. For example, one potentially
important addition to the antimalarial pharmacopoeia, lumefantrine-artemether
(Co-artem), is not approved for use in the very groups that are likely to need
it the most, children <10 kg in weight and pregnant women, making the drug
either of limited value or forcing health care providers (and patients) to
bear the risk of off-label use.
In addition to use for treatment of acute illness, preventive use of antimalarial drugs is being promoted for both pregnant women and infants (see below). The safety profile of drugs needs to be even more favorable to justify their use among otherwise healthy individuals, as the risk:benefit ratio is very different from that among acutely ill patients.
Combination therapy
Much has been written about combination therapy
(White et al., 1999;
White, 1999
;
Bloland et al., 2000
;
Nosten and Brasseur, 2002
).
There is also a review on combination therapy in this issue
(Olliaro and Taylor, 2003
).
Combining antimalarial drugs, especially when one of the components is an
artemisinin compound, offers increased efficacy and the potential for
inhibition of development of resistance and reductions in overall
transmission, at least in some environments. Use of drugs in combination
(especially artemisinin-containing combinations or ACTs) is currently the
World Health Organization's recommended strategy for coping with drug
resistance globally (WHO,
2001
).
Unfortunately, as is true for any drug (whether in combination or not,
whether coformulated or coadministered), the mere existence of a new treatment
does not guarantee that the treatment will have any public health impact
(Bloland et al., 2000). These
therapies must not only exist, but must be affordable, accessible and
acceptable to the end user. Additionally, the end-user must be able to take
them in correct quantities and for correct amounts of time. They must be
sufficiently safe, especially among users in the highest risk groups. Finally,
they must be robust enough in terms of their ability to withstand the misuse
that is likely to occur and the selective pressure that this misuse will place
on the parasite.
The decline of the public health system
In much of the region, public health infrastructure is inadequate to fully
meet existing needs (Kager,
2002; Moerman et al.,
2003
). This manifests in many ways that affect the provision and
use of antimalarial agents. Relatively few health facilities have or use
laboratory-based diagnostic tests for identifying patients with malaria
infections, therefore the majority of febrile patients receive malaria
treatment, regardless of whether or not they are actually infected (see
section on diagnosis below). Staff training and motivation can be poor and
many facilities operate without reliable access to medicines, electricity or
clean water (Gilson et al.,
1994
; Isra et al.,
2000
).
Nonetheless, the formal public health sector provides an important service
to communities, especially when home-based treatments for fever fail.
Strategies to address improvements in public health sector should address the
specific reasons why people might choose to avoid those facilities, such as
poor quality service, leakage of drugs for private resale, informal patient
charges, mismanagement of patient user fees, distance to facilities, lack of
drugs and other desired services, cost and lengthy waiting times
(Agyepong, 1995;
Baume et al., 2000
;
Lindblade et al., 2000
;
McPake et al., 1999
;
Mumba et al., 2003
;
Ndyomugyenyi et al., 1998
;
Nyamongo, 2002
;
Tarimo et al., 2000
;
Williams et al., 1999
).
The growing importance of the private sector
In Africa, private sector sources of antimalarial drugs often refer not
only to officially recognized businesses, such as private pharmacies or
general merchandisers, but also to informal sources, such as small kiosks or
even itinerant drug sellers. Regardless of the permanence or formality of the
shop, the importance of private sector sources of antimalarial drugs is
substantial in many African communities
(Adome et al., 1998;
Baume et al., 2000
;
Gilson et al., 1994
;
Ndyomugyenyi et al., 1998
;
Thera et al., 2000
). In some
studies, as much as 60% of patients (or more) seeking help for febrile illness
receive medicines from the private sector
(McCombie, 1996
;
WHO/UNICEF, 2003
; S. P.
Kachur, CDC, 2003, unpublished data).
The popularity of the private sector is, in part, a result of the poor
state of the public sector, but also because private sector outlets tend to be
more numerous, closer to home, offer rotating credit schemes, have drugs in
stock, and involve less time to obtain the desired treatments
(Armstrong-Schellenberg et al.,
2001; Marsh and Mutemi,
1997
; Molyneux,
2002
; Ongore and Nyabola, 1996;
Reynolds-Whyte and Birungi,
2000
). These outlets also tend to interact with the customer in a
friendlier fashion than health care workers interacting with patients.
Unfortunately, it has been well established that the private sector is poor at
providing appropriate advice, complete doses, or even the correct drug for the
problem (Djimde et al., 1998
;
Mwenesi, 1994
;
Massele et al., 1998
;
Oketch-Rabah et al.,
1998
).
Due to the importance of private sector sources of medicines, many groups
are investigating ways to improve the process by which these drug sellers
provide drugs (Marsh et al.,
1999; Reynolds-Whyte and
Birungi, 2000
). In Kenya, providing shop keepers with specific
training on how best to provide malaria medicines and what advice to give
patients resulted in an increase in the appropriate use of over-the-counter
chloroquine by at least 62% (Marsh et al.,
1999
). Other efforts are aimed at social marketing of licensed or
franchised drug shops where provision of quality treatment advice is available
and a higher degree of quality assurance can be achieved (for example, see
http://www.msh.org/features/gates/kenya-release.html).
It is now being recognized that the educational system could be used to target
messages about antimalarials and the need for prompt and effective treatment,
supplementing efforts at improving health care through the public system
(Bundy et al., 2000
;
Geissler et al., 2001
). Some
novel programs are now being conducted that focus on training school children
in the appropriate use of drugs (van der
Geest and Geissler, 2003
). Many countries are now facing the
choice between continuing to support malaria treatment primarily through a
failing public health system or divert those needed funds to improve access
and use of malaria medicines through a largely uncontrollable private sector,
or to try to do both and run the risk of doing neither well.
Pre-packaging medicines
To improve both the private sector's ability to provide malaria drugs
correctly as well as the likelihood that patients will take the correct dose
and complete the full regimen, schemes have been developed to pre-package
medicines for specific age ranges. In most circumstances, such pre-packaging
has not only been well received by the end-users but well-designed drug
packages have increased patient compliance by, on average, 20%
(Yeboah-Antwi et al., 2001;
Pagnoni et al., 1997
). Initial
findings are encouraging for the use of pre-packaged antimalarial drugs. In a
recent study in Burkino Faso, mothers could recognize and treat malaria in a
prompt and correct manner, given appropriate training and adequately packaged
drugs (Sirima et al.,
2003
).
Pre-packaging has its own limitations. For logistical reasons related to drug management and supply, a small number of packages are created, covering broad age ranges (such as for patients under 1 year, 1 to 6 years, 7 to 11 years, and 12 years and above). This situation raises the possibility of over- or under-dosing at the extremes of the age range, especially among populations where malnutrition is prevalent.
Labeling of medicines
Packaging of pharmaceuticals, malaria drugs included, is woefully
inadequate given the settings in which they are used (C. Goodman, London
School of Hygiene and Tropical Medicine, personal communication). When drugs
are given with printed information, that information is typically written
using complicated or technical language, or written in a language foreign to
the end user, or of little use to a predominantly illiterate population. More
often, especially for drugs provided through the private sector, no
information is given at all: pills and syrups are provided to the patient
wrapped in slips of paper or unmarked bottles. Due to their lower costs,
medicines are often bought in bulk jars that are labeled with nothing more
than `Use as directed by physician' (if labeled at all), leaving both vendor
and patient clueless as to how to properly dose the medicine.
Increasingly, these shortcomings are being recognized and addressed. Efforts to produce pre-packaged medicines are often accompanied by efforts to improve patient information, including graphic representations of proper use for illiterate patients and written information in a locally appropriate language. These innovations, however, add to the cost of the drug and, particularly within the private sector, may not be sufficient to ensure adequate patient education.
Integrated management of childhood illness (IMCI)
IMCI is an algorithm that, when used properly, assists health care workers
to identify and treat the most common childhood illnesses on the basis of
clinical signs and symptoms. The algorithm is intended to rationalize the
diagnosis and treatment of these illnesses in settings where health care
workers are minimally trained and have poor or non-existent access to
laboratory or radiographic diagnosis
(Perkins et al., 1997). This
approach is intended to be an improvement over an unstructured clinical
diagnostic approach in that it encourages health care workers to spend more
time and effort conducting a more thorough assessment of children.
This approach does not change malaria diagnosis much, as any child with fever or history of fever is assumed to have malaria, even in areas where as little as 5% of febrile children actually have parasites on blood smear. The result is considerable misdiagnosis and unnecessary treatment. In a health facility survey recently conducted in Tanzania, for example, a greater proportion of children with IMCI-diagnosed `malaria' was found to be aparasitemic than among children with `malaria' diagnosed using traditional, non-structured clinical diagnosis (62% vs. 40%, respectively) (L. Causer, CDC, 2003, unpublished data).
Improved access and use of laboratory-based diagnostics
As mentioned previously, the prevailing method for diagnosing malaria in
sub-Saharan Africa is by clinical impression, which, in turn, typically
amounts to treating all fevers as malaria. The inaccuracies of this method are
well known. In various studies of clinical diagnosis of malaria using IMCI,
the sensitivity of clinical diagnosis (i.e. the proportion of clinically
diagnosed malaria patients that actually have malaria infection) can range
from 87% to 100%. The specificity of clinical diagnosis (the proportion of all
patients that do not get a diagnosis of malaria who actually do not have
malaria infection) can range from 0% to 8%
(Perkins et al., 1997; Weber
et al., 1996).
Laboratory-based diagnostic tests can improve this situation dramatically;
however, access to laboratory diagnosis is rare. Even in facilities with
laboratories capable of performing diagnostic tests, the results of these
tests are often ignored (Barat et al.,
1999).
The advent of simple-to-use, rapid-diagnostic tests (RDTs) for malaria
holds the promise of more definitive diagnosis occurring even in settings
lacking laboratory capacity (Moody,
2002). Under controlled conditions, RDTs reportedly have very high
sensitivity and specificity (ranging between 81% and 100% for both), although
their sensitivity drops with very low parasite densities
(Moody, 2002
). Although South
Africa uses RDTs for primary malaria diagnosis (and requires laboratory-based
confirmation before treatment), and other countries have used RDTs during
emergency situations, these tests are currently far too expensive for the
majority of endemic countries in Africa to sustain (US$0.80-2.50 per test)
(National Research Council,
2003
). Nonetheless, in some settings, microscopic diagnosis of
malaria has been shown to be cost-effective, even cost-saving
(Jonkman et al., 1995
).
Home-based management of malaria/'community IMCI'
There is increasing interest in pushing malaria treatment closer to home,
or even to within the home (Winch et al.,
2002). The argument in favor of this strategy is based on the
assertions that (i) malaria infections can progress to severe or fatal illness
very rapidly, (ii) many children die within the home without visiting a health
facility and (iii) a majority of treatment already occurs in the home with
medicines either bought from shops or left over from previous clinic trips.
Although there is no single accepted definition of what exactly home-based
malaria therapy actually is, the general desire is to vastly improve access to
efficacious medicines at the most peripheral level (in terms of availability
and price) and to increase community members' knowledge about how to properly
use them.
A number of studies have shown that such approaches can be highly
effective. In Ethiopia, for example, local mothers were trained to provide
their neighbors within their village with information on how to identify
likely malarial illness and to supply chloroquine packaged with pictorial
instructions for appropriate use. This strategy led to a reduction of 41% in
the under-five mortality rate over 2 years, compared to villages with the more
typical community health workers who were not specifically supplied with
malaria treatment (Kidane and Morrow,
2000).
Intermittent Preventive Treatment for pregnant women (IPT) and
infants (IPTi)
A relatively new approach to preventing the effects of malaria in pregnancy
has been developed and is being actively promoted. In this strategy, pregnant
women are given full treatment doses of an antimalarial drug regularly during
pregnancy regardless of malaria infection or illness status (Intermittent
Preventive Treatment or IPT). Such treatment should occur, at a minimum, once
in the second and once in the third trimester of pregnancy, although in most
settings, more frequent treatment is advisable
(WHO, 2002). This strategy has
been associated with substantial reductions in maternal anemia, fetal loss and
low birth weight and, because low birth weight is a primary risk factor for
infant mortality, IPT may improve child survival
(WHO/UNICEF, 2003
). A similar
approach, Intermittent Protective Treatment for Infants (IPTi), has been
proposed and is currently being evaluated extensively. In this strategy,
children are given periodic treatment doses of antimalarial drugs with the aim
of reducing morbidity and mortality during infancy. The only published study
of this strategy suggests that, when linked to a child's routine immunization
schedule, IPTi resulted in a decrease in clinical malaria and severe anemia of
about 50-60% (Schellenberg et al.,
2001
).
Global Fund for AIDS, Tuberculosis and Malaria (GFATM) and other
financing schemes
The newer malaria medicines, including artemisinin-containing combination
therapies (ACTs), are substantially more expensive than the single-drug
treatments in common current usage (e.g. US$0.15-0.20 for an adult dose of
chloroquine or SP compared with US$1.20-2.40 for ACTs). The ability of most
African economies to sustain these increased malaria treatment costs is
limited. The GFATM, which delivered its first grants in 2001, has provided
substantial funds to a number of countries in sub-Saharan Africa to support
malaria control activities (see
www.globalfundatm.org).
Some countries have applied these funds to changing their antimalarial drug
policies, including the purchase of ACTs. The World Bank has indicated that
its loans could be used to buy malaria medicines. In other situations,
non-governmental organizations (NGOs) have offered to supply governments with
ACTs.
While these mechanisms offer some hope for governments not otherwise able
to afford the expensive, new medicines, there are lingering concerns over
financial sustainability. Concerns over the longevity of the Global Fund have
already been raised (Kapp,
2002). Countries are reluctant to take on additional national debt
for malaria drugs. While donations via NGOs can be helpful in the
short-term for specific situations, the long-term sustainability of those
donations is doubtful.
Finally, all of these mechanisms are best suited to providing drugs via the public health sector. None of these funding initiatives have identified a way to provide free or heavily subsidized malaria treatment via the private sector, which is relied upon so extensively in sub-Saharan Africa.
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Conclusions |
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While a few attempts at reconciling these divergent paradigms have occurred (pre-packaging; improved labeling and instructions; improved education of private sector drug vendors), far more needs to be done in order to ensure that new, highly efficacious treatments are in fact, programmatically effective and, therefore, offer the best chance of contributing positively towards reducing the burden of malaria in sub-Saharan Africa. This will be likely to require investment in large-scale studies to ascertain the likely impact of these strategies, both to illustrate improvements in health outcomes associated with wider and easier access to antimalarials as well as to better understand the implications of this wider and easier access to antimalarials might have on development of drug resistance.
It is clear, however, that Africa cannot and will not wait until everything is known before moving ahead. The risk is real that the promise of these new therapies might be squandered by deploying them in a `business as usual' fashion. But by being cognizant of the implications of the realities of the environment in which antimalarial drugs are used in sub-Saharan Africa and deploying these various new treatments in a manner that maximizes programmatic effectiveness, the positive impact of these promising new therapies can be realized.
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References |
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---|
Adome, O. R., Whyte, S. R., Ortenblad, L., Ezati, E., Nsabagasani, X., Owor, J. and Turinde, A. K. (1998). The community epidemiology of drug use: A case of three districts in Uganda. In Proceedings of Workshop on People and Medicines in East Africa, 16-20 November 1998 (ed. W. Geissler and L. Meinert). Copenhagen: Danish Bilharziasis Laboratory.
Agyepong, I. (1995). Improving malaria control in the context of health sector reform. Technical Report prepared for the WHO/TDR. Geneva: World Health Organisation.
Armstrong-Schellenberg, J., Abdulla, S., Nathan, R., Mukasa, O., Marchant, T., Kikumbih, N., Mushi, A., Mponda, H., Minja, H., Mshinda, H., Tanner, M. and Lengeler, C. (2001). Effect of large-scale social marketing of insecticide-treated nets on child survival in rural Tanzania. Lancet 357,1241 -1247.[CrossRef][Medline]
Barat, L., Chipipa, J., Kolczak, M. and Sukwa, T.
(1999). Does the availability of blood slide microscopy for
malaria at health centers improve the management of persons with fever in
Zambia? Am. J. Trop. Med. Hyg.
60,1024
-1230.
Baume, C., Helitzer-Allen, D. and Kachur, P. (2000). Patterns of care for childhood malaria in Zambia. Soc. Sci. Med. 51,1491 -1503.[CrossRef][Medline]
Bloland, P. B. and Ettling, M. (1999). Making malaria-treatment policy in the face of drug resistance. Annu. Trop. Med. Parasitol. 93,5 -23.[Medline]
Bloland, P. B., Ettling, M. and Meek, S. (2000). Combination therapy for malaria in Africa: Hype or Hope? Bull. WHO 78,1378 -1388.[Medline]
Bundy, D. A. P., Lwin, S., Osika, J. S., McLaughlin, J. and Pannenborg, C. O. (2000). What should schools do about malaria? Parasitol. Today 16,181 -182.[CrossRef][Medline]
Deming, M. S., Gayibor, A., Murphy, K., Jones, T. S. and Karsa, T. (1989). Home treatment of febrile children with antimalarial drugs in Togo. Bull. WHO 67,695 -700.[Medline]
Djimde, A., Plowe, C., Diop, S., Dikco, A., Wellems, T. and
Doumbo, O. (1998). Use of antimalarial drugs in Mali: Policy
versus reality. Am. J. Trop. Med. Hyg.
59,376
-379.
Geissler, P. W., Meinert, L., Prince, R., Nokes, C.,
Aagaard-Hansen, J., Jitta, J. and Ouma, J. H. (2001).
Self-treatment by Kenyan and Uganda schoolchildren and the need for
school-based education. Health Pol. Plan.
16,362
-371.
Gilson, L., Alilio, M. and Heggenhougen, K. (1994). Community satisfaction with primary health care services: An evaluation undertaken in the Morogoro Region of Tanzania. Soc. Sci. Med. 39,767 -780.[CrossRef][Medline]
Isra, S. M., Razum, O., Ndiforchu, V. and Martiny, P. (2000). Coping strategies of health personnel during economic crisis: A case study from Cameroon. Trop. Med. Int. Health 5,288 -292.[CrossRef]
Jonkman, A., Chibwe, R. A., Khoromana, C. O., Liabunya, U. L., Chaponda, M. E., Kandiero, G. E., Molyneux, M. E. and Taylor, T. E. (1995). Cost-saving through microscopy-based versus presumptive diagnosis of malaria in adult outpatients in Malawi. Bull. WHO 73,223 -227.[Medline]
Kager, P. A. (2002). Malaria control: constraints and opportunities. Trop. Med. Int. Health 7,1042 -1046.[CrossRef][Medline]
Kapp, C. (2002). Global Fund faces uncertain future as cash runs low. Lancet 360, 1225.[CrossRef][Medline]
Kidane, G. and Morrow, R. H. (2000). Teaching mothers to provide home treatment of malaria in Tigray, Ethiopia: a randomised trial. Lancet 356,550 -555.[CrossRef][Medline]
Krause, G. and Sauerborn, R. (2000). Comprehensive community effectiveness of health care. A study of malaria treatment in children and adults in rural Burkina Faso. Ann. Trop. Paediatr. 20,273 -282.[Medline]
Lindblade, K., O'Neill, D., Mathanga, D., Katungu, J. and Wilson, M. (2000). Treatment for clinical malaria is sought promptly during an epidemic in a highland region of Uganda. Trop. Med. Int. Health 5,865 -875.[CrossRef][Medline]
Marsh, V. and Mutemi, W. (1997). A community educational intervention to optimize the home use of shop-bought antimalarial drugs in the management of uncomplicated childhood fevers. Technical Report prepared for the KEMRI/CRC/DVBD. Nairobi: Kenya Medical Research Institute.
Marsh, V., Mutemi, W., Muturi, J., Haaland, A., Watkins, W., Otieno, G. and Marsh, K. (1999). Changing home treatment of childhood fevers by training shop keepers in rural Kenya. Trop. Med. Int. Health 4,383 -389.[CrossRef][Medline]
Massele, A., Nsimba, S. E. D., Warsame, M. and Tomson, G. (1998). A survey of sources, availability and use of antimalarial drugs in households and drug stores in Kibaha, Tanzania. In Proceedings of Workshop on People and Medicines in East Africa, 16-20 November 1998 (ed. W. Geissler and L. Meinert). Copenhagen: Danish Bilharziasis Laboratory.
McCombie, S. C. (1996). Treatment seeking for malaria: a review of recent research. Soc. Sci. Med. 43,933 -945.[CrossRef][Medline]
McPake, B., Asiimwe, D., Mwesigye, F., Ofumbi, M., Ortenblad, L., Streefland, P. and Turinde, A. (1999). Informal economic activities of public health workers in Uganda: implications for quality and accessibility of care. Soc. Sci. Med. 49,849 -865.[CrossRef][Medline]
Moerman, F., Lengeler, C., Chimumbwa, J., Talisuna, A., Erhart, A., Coosemans, M. and D'Alessandro, U. (2003). The contribution of health-care services to a sound and sustainable malaria-control policy. Lancet Inf. Dis. 3, 99-102.[CrossRef][Medline]
Molyneux, C. S., Murira, G., Masha, J. and Snow, R. W. (2002). Intra-household relations and treatment decision-making for childhood illness: A Kenyan case study. J. Biosoc. Sci. 34,109 -131.[Medline]
Moody, A. (2002). Rapid diagnostic tests for
malaria parasites. Clin. Microbiol. Rev.
15, 66-78.
Mumba, M., Visschedijk, J., van Cleeff, M. and Hausman, B. (2003). A Piot model to analyse case management in malaria control programmes. Trop. Med. Int. Health 8, 544-551.[CrossRef][Medline]
Mwenesi, H. (1994). The role of drug delivery systems in health care: the case of self-medication. African J. Health Sci. 1,43 -48.
National Research Council (2003). Malaria Control During Mass Population Movements and Natural Disasters (ed. P. B. Bloland and H. A. Williams), pp.60 -62. Washington, DC: National Academies Press.
Ndyomugyenyi, R., Neema, S. and Magnussen, P. (1998). The use of formal and informal services for antenatal care and malaria treatment in rural Uganda. Health Pol. Plan. 13,94 -102.[Abstract]
Nosten, F. and Brasseur, P. (2002). Combination therapy for malaria: the way forward? Drugs 62,1315 -1329.[Medline]
Nyamongo, I. (2002). Health care switching behavior of malaria patients in a Kenyan rural community. Soc. Sci. Med. 54,377 -386.[CrossRef][Medline]
Oketch-Rabah, H. A., Oduol, E., Oluka, M. A. and Nyamwaya, D. (1998). Use of traditional and pharmaceutical medicines in Kenya: The case of Kisumu and Rachuonyo Districts in Luo Nyanza. In Proceedings of Workshop on People and Medicines in East Africa, 16-20 November 1998 (ed. W. Geissler and L. Meinert). Copenhagen: Danish Bilharziasis Laboratory.
Olliaro, P. L. and Taylor, W. R. J. (2003). Antimalarial compounds: from bench to bedside. J. Exp. Biol. 3753-3759.
Ongore, D. and Nyabola, L. (1998). The role of shops and shopkeepers in malaria control. In Proceedings of Workshop on People and Medicines in East Africa, 16-20 November 1998 (ed. W. Geissler and L. Meinert). Copenhagen: Danish Bilharziasis Laboratory.
Pagnoni, F., Convelbo, N., Tiendrebeogo, J., Cousens, S. and Esposito, F. (1997). A community-based programme to provide prompt and adequate treatment of presumptive malaria in children. Trans. R. Soc. Trop. Med. Hyg. 91,512 -517.[Medline]
Perkins, B. A., Zucker, J. R., Otieno, J., Jafari, H. S., Paxton, L., Redd, S. C., Nahlen, B. L., Schwartz, B., Oloo, A. J., Olango, C., Gove, S. and Campbell, C. C. (1997). Evaluation of an alogrithm for integrated management of childhood illness in an area of Kenya with high malaria transmission. Bull. WHO 75, 33-42.[Medline]
Robb, A., Sukwa, T. and Walker, O. (2003).Framework for developing, implementing and updating national antimalaria treatment policy: a guide for country malaria control programmes. AFR/MAL/03.02. Brazzaville, Republic of Congo: World Health Organization, Regional Office for Africa.
Ruebush, T., Kern, M., Campbell, C. and Oloo, A. (1995). Self-treatment of malaria in a rural area of western Kenya. Bull. WHO 73,229 -236.[Medline]
Reynolds-Whyte, S. and Birungi, H. (2000). The business of medicines and the politics of knowledge. In Global Health Policy, Local Realities (ed. L. M. Whiteford and L. Manderson), pp. 127-148. Boulder: Lynne Rienner.
Schellenberg, D., Menendez, C., Kahigwa, E., Aponte, J., Vidal, J., Tanner, M., Mshinda, H. and Alonso, P. (2001). Intermittent treatment for malaria and anemia control at time of routine vaccinations in Tanzanian infants: a randomized, placebo-controlled trial. Lancet 357,1471 -1477.[CrossRef][Medline]
Sirima, B. S., Konate, A., Tiono, A. B., Convelbo, N., Cousens, S. and Pagnoni, F. (2003). Early treatment of childhood fevers with pre-packaged antimalarial drugs in the home reduces severe malaria morbidity in Burkino Faso. Trop. Med. Int. Health 8, 133-139.[CrossRef][Medline]
Slutsker, L., Chitsulo, L., Macheso, A. and Steketee, R. W. (1994). Treatment of malaria fever episodes among children in Malawi: results of a KAP survey. Trop. Med. Parasitol. 45, 61-64.[Medline]
Tarimo, D. S., Lwihula, G. K., Minjas, J. N. and Bygbjerg, I. C. (2000). Mothers' perceptions and knowledge on childhood malaria in the holoendemic Kibaha district, Tanzania: implications for malaria control and the IMCI strategy. Trop. Med. Int. Health 5, 179-184.[CrossRef][Medline]
Thera, M. A., D'Alessandro, U., Thiero, M., Ouedraogo, A., Packou, J., Souleymane, O. A. D., Fane, M., Ade, G., Alvez, F. and Doumbo, O. (2000). Child malaria treatment practices among mothers in the district of Yanfolila, Sikasso region, Mali. Trop. Med. Int. Health 5,876 -881.[CrossRef][Medline]
van der Geest, S. and Geissler, P. W. (2003). Editorial: Should medicines be kept away from children? Trop. Med. Int. Health 8,97 -99.[CrossRef][Medline]
Weber, M. W., Mulholland, E. K., Jaffar, S., Troedsson, H., Gove, S. and Greenwood, B. M. (1997). Evaluation of an algorithm for the integrated management of childhood illness in an area with seasonal malaria in the Gambia. Bull. WHO 75, 25-32.[Medline]
White, N. J. (1999). Delaying antimalarial drug resistance with combination chemotherapy. Parassitologia 41,301 -308.[Medline]
White, N. J., Nosten, F., Looareesuwan, S., Watkins, W. M., Marsh, K., Snow, R. W., Kokwaro, G., Ouma, J., Hien, T. T., Molyneux, M. E. et al. (1999). Averting a malaria disaster. Lancet 353,1965 -1967.[CrossRef][Medline]
Williams, H., Kachur, P., Nalwamba, C., Hightower, A., Simoonga, C. and Mphande, P. (1999). A community perspective on the efficacy of malaria treatment options for children in Lundazi District, Zambia. Trop. Med. Int. Health 4, 641-652.[CrossRef][Medline]
Winch, P. J., Leban, K., Casazza, L., Walker, L. and Pearcy,
K. (2002). An implementation framework for household and
community integrated management of childhood illness. Health Pol.
Plan. 17,345
-353.
WHO (1973). Chemotherapy of malaria and resistance to antimalarials. Report of a WHO scientific group. Technical Report Series #529. Geneva: World Health Organisation.
WHO (1986). WHO Expert Committee on Malaria, Eighteenth Report. Technical Report Series #735. Geneva: World Health Organisation.
WHO (1996). Assessment of therapeutic efficacy of antimalarial drugs for uncomplicated falciparum malaria in areas with intense transmission. WHO/MAL/96.1077. Geneva and Brazzaville: World Health Organisation.
WHO (1997). Integrated Management of Childhood Illnesses Adaptation Guide. Part 2. C. Technical basis for adapting clinical guidelines, feeding recommendations, and local terms. Working Draft Version 3. Division of Child Health and Development, World Health Organisation, pp. 49-51. Geneva: World Health Organisation.
WHO (2001). Antimalarial Drug Combination Therapy. Report of a WHO Technical Consultation, 4-5 April, 2001. WHO/CDS/RBM/2001.35. Geneva: World Health Organisation.
WHO (2002). Strategic framework for malaria control during pregnancy in the WHO Africa Region. Final Draft document, Nov 1, 2002. Geneva: World Health Organisation.
WHO/UNICEF (2003). The African Malaria Report, 2003. (WHO/CDS/MAL/2003.1093) Geneva: World Health Organization.
Yeboah-Antwi, K., Gyapong, J. O., Asare, I. K., Barnish, G., Evans, D. B. and Adjei, S. (2001). Impact of prepackaging antimalarial drugs on cost to patients and compliance with treatment. Bull. WHO 79,394 -399.[Medline]
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