Malaria Journal

BioMed Central

Open Access

Research

A cost-effectiveness analysis of artemether lumefantrine for

treatment of uncomplicated malaria in Zambia
Pascalina Chanda1, Felix Masiye*2, Bona M Chitah3, Naawa Sipilanyambe1,
Moonga Hawela1, Patrick Banda1 and Tuoyo Okorosobo4
Address: 1National Malaria Control Centre, Box 32 509, Lusaka, Zambia, 2Department of Economics, University of Zambia, Lusaka, Zambia,
3Ministry of Health, Lusaka, Zambia and 4Regional Office for Africa, World Health Organization, Cit du Djou, Brazzaville, Congo
Email: Pascalina Chanda - chandap@nmcc.org.zm; Felix Masiye* - felix_masiye@harvard.edu; Bona M Chitah - mukoshya@mail.zamtel.zm;
Naawa Sipilanyambe - nsipilan@yahoo.co.uk; Moonga Hawela - mhawela@nmcc.org.zm; Patrick Banda - patrickbnd@yahoo.co.uk;
Tuoyo Okorosobo - okorosobot@na.afro.who.int
* Corresponding author

Published: 21 February 2007

Malaria Journal 2007, 6:21

doi:10.1186/1475-2875-6-21

Received: 23 August 2006

Accepted: 21 February 2007

This article is available from: http://www.malariajournal.com/content/6/1/21

2007 Chanda et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background: Malaria remains a leading cause of morbidity, mortality and non-fatal disability in Zambia,
especially among children, pregnant women and the poor. Data gathered by the National Malaria Control
Centre has shown that recently observed widespread treatment failure of SP and chloroquine precipitated
a surge in malaria-related morbidity and mortality. As a result, the Government has recently replaced
chloroquine and SP with combination therapy as first-line treatment for malaria. Despite the acclaimed
therapeutic advantages of ACTs over monotherapies with SP and CQ, the cost of ACTs is much greater,
raising concerns about affordability in many poor countries such as Zambia. This study evaluates the costeffectiveness analysis of artemether-lumefantrine, a version of ACTs adopted in Zambia in mid 2004.
Methods: Using data gathered from patients presenting at public health facilities with suspected malaria,
the costs and effects of using ACTs versus SP as first-line treatment for malaria were estimated. The study
was conducted in six district sites. Treatment success and reduction in demand for second line treatment
constituted the main effectiveness outcomes. The study gathered data on the efficacy of, and compliance
to, AL and SP treatment from a random sample of patients. Costs are based on estimated drug, labour,
operational and capital inputs. Drug costs were based on dosages and unit prices provided by the Ministry
of Health and the manufacturer (Norvatis).
Findings: The results suggest that AL produces successful treatment at less cost than SP, implying that
AL is more cost-effective. While it is acknowledged that implementing national ACT program will require
considerable resources, the study demonstrates that the health gains (treatment success) from every
dollar spent are significantly greater if AL is used rather than SP. The incremental cost-effectiveness ratio
is estimated to be US$4.10. When the costs of second line treatment are considered the ICER of AL
becomes negative, indicating that there are greater resource savings associated with AL in terms of
reduction of costs of complicated malaria treatment.
Conclusion: This study suggests the decision to adopt AL is justifiable on both economic and public health
grounds.

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Background
Malaria remains a leading cause of morbidity, mortality
and non-fatal disability in Zambia, especially among children, pregnant women and the poor. The disease burden
caused by malaria in Zambia has grown steadily over the
recent decades. Malaria is endemic in most parts of Zambia although rural areas and poor urban cities tend to bear
a disproportionate share of malaria transmission and burden. Estimates based on the Health Information System
(HIS) suggest that malaria incidence has increased from
121.5 per 1,000 in 1976 to 429.3 per 1000 in 2003 [1,2].
Recent statistics show that in 2003 some 3.5 million
malaria cases were attended to at public health facilities.
In the same year, malaria accounted for 23% of all deaths
occurring at hospitals, making it the leading cause of
death in the country [1,3]. Malaria, especially in its severe
form, affects people in more ways than these metrics can
measure. For example, malaria is known to impair the
general immunity of children, leaving them susceptible to
other causes of illness and death. Malaria also affects the
cognitive ability of individuals [4]. The difficulties with
the validity of these numbers notwithstanding, malaria is
still considered to be a major health problem that affects
the widest section of the Zambian population.
Over the recent past, health information and various surveys have revealed that widespread treatment failure precipitated a rise in malaria mortality and morbidity.
National data collected by the National Malaria Control
Centre (NMCC) confirmed that a considerable decline in
the therapeutic efficacy of sulphadoxine-pyrimethamine
(SP) and chloroquine (CQ) was responsible for the high
and widespread treatment failure rates [5]. This situation
had significant implications since treatment with antimalarial drugs has been the only tool used in fighting
malaria from the late 1970s. In terms of prospects for
young children, most of whom are treated at home, failure of the only possible defence against malaria meant rising mortality.
Widespread treatment failure was an Africa-wide phenomenon which was observed from the late 1980's and
spread rapidly from then on. The evidence from several
studies pointed unequivocally to growing drug resistance
and childhood mortality [6]. In response to growing criticism against the use of failing monotherapies, the World
Health Organization and Roll-Back Malaria led a global
campaign to replace SP and chloroquine with artemesinin
combination therapies (ACT) as first-line treatment [7].
To date, not all countries in Africa have implemented
ACTs as first-line treatment for malaria. The two most
widely considered ACT brands in Africa presently are the
fixed-dose combination artemether-lumefantrine (AL)
and the co-packaged combination of amodiaquine and
artesunate (AQ+AS). These combinations have proved

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highly efficacious in carefully controlled phase III clinical

trials in areas with moderate to high levels of SP or CQ
resistance in Africa [7].
In 2004, Zambia adopted AL as the new first-line drug for
treatment of malaria in all public health facilities. The policy pronouncement was informed by the widely
acclaimed efficacy of ACTs without a comprehensive economic evaluation. From a therapeutic point of view artemesinin-based products have been shown to have
important advantages: if they are used in combination
with other anti-malarial therapies, the rate at which resistance emerges will be slowed down. In addition, ACTs
clear parasites faster and more completely than classical
drugs [8,9]. In this way, they reduce treatment failure and
a recurrence of new malaria episodes thereby reducing the
probability of progression to severe malaria. In this way,
ACTs, avert malaria mortality and various forms of debilitating sequelae that are associated with episodes of severe
malaria especially on children [8]. Unfortunately, ACTs
are significantly more expensive than the existing antimalarials. Thus, from an economic point of view, the
question arises if the therapeutic benefits of ACTs outweigh the extra cost of ACTs. This economic framework
embodies in cost-effectiveness analysis addresses the
question of whether, given a fixed budget, the Zambian
health care system could achieve better health gains with
ACTs or with the existing anti-malarial drugs, namely SP.
One of the main concerns with scaling up implementation ACTs in Zambia and other African countries has been
the cost [10]. Given the difficult trade-offs that the Zambian government faces in terms of allocating resources
across a broad disease spectrum, effectiveness alone is
unlikely to be a sufficient premise for initiating a new
intervention. In this particular case, given the high cost of,
a greater need arises to ensure that there is efficiency and
effectiveness in the diagnosis of malaria and its treatment
with the usage of Artemether-lumefantrine. In Zambia, an
intense national debate emerged in the wake of this new
policy. Opponents and pessimists doubted the cost-effectiveness of ACTs given their high prices and also the weaknesses in the diagnostic and prescribing capacities of the
health system. This study sought to generate systematic
evidence on the clinical effects, cost and cost-effectiveness
of AL from an actual practice routine malaria management framework. The purpose of this survey was to assess
the cost-effectiveness of AL in reference to SP for the treatment of uncomplicated malaria.

Methods and data

This study was designed to capture data on health outcomes from a real health setting. Rather than employ a
randomized control trial approach, the study employed
data generated by the health system through its routine

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systems. The main rationale for taking this approach was

that it is unlikely that even the introduction of ACTs was
going to interfere with the current treatment protocol
which requires presumptive treatment of most febrile
cases in children. In Zambia, this practice is often
extended to adults. Treatment practices clearly affect the
cost-effectiveness of ACTs. In this context, it is considered
crucial to test a cost-effectiveness model that is based on
data generated from actual practice. Another important
factor to consider for cost-effectiveness analysis is that AL
in Zambia was introduced in a context of very low coverage of prevention strategies. According to the 2001/2
Demographic and Health Survey (DHS), the national coverage of insecticide treated bed-nets for children under the
age of five years in Zambia is now only 23% after a mass
distribution campaign that took place after the period of
this survey [11]. Therefore, the cost-effectiveness analysis
conducted here should be interpreted in this context that
the underlying incidence of malaria in the population is
unlikely to have changed significantly. Nonetheless, the
main purpose was to demonstrate the cost-effectiveness of
AL as a first-line drug.
Study design and population
This study was designed around building a data base capturing the short-term effects and cost of treating patients
with a new malaria drug. Thus, the study population
included all patients presenting with suspected malaria
visiting outpatient facilities (health centres). To achieve
this, health staff at the study sites were thoroughly trained
to record data on diagnosis and treatment from all
patients suspected of having malaria into a speciallydesigned register. The data on diagnosis, temperature,
treatment provided, outcome within 28 days, follow up
action and some basic patient characteristics were
recorded into these registers. Consistent with the perspective taken, malaria was defined using the standard Ministry of Health Malaria Case Management Manual as
operationalised by health workers. Further, Data on all
the malaria attendances from the period 2000 to 2004
(so-called retrospective data) were retrieved from registers
at the study facilities. These represented both confirmed
and non-confirmed cases.

Ideally, all patients are requested to report for a review 10

days after treatment to ascertain their response to treatment. However, less than 10% of the patients turned up,
implying that only a survey-based method would yield
valid and reliable data on the therapeutic effects of AL and
associated patient compliance. Thus, data on treatment
outcome and patient compliance within a 28-day period
were compiled in a follow-up survey on a sample from the
same population that was conducted during the same
time period. During these surveys, parasitological confirmation of cure was performed using microscopy. Stand-

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ard WHO protocols were followed in conducting the

efficacy of anti-malarials as well as compliance surveys.
Efficacy and compliance surveys were handled by an independent team from the National Malaria Control Centre
to ensure validity. Details of the study and protocol are
available at the National Malaria Control Centre. Full
details on the procedure of efficacy and compliance determination have been published elsewhere [12-14]. Finally,
previous evaluation surveys [15,16] provided the applicable Zambian estimates for efficacy and compliance to the
previous anti-malarial regimens (SP) in Zambia.
Survey administration and data handling
A total of six study districts were selected by the NMCC for
the study; Kabwe, Chongwe, Chipata, Kalomo, Chingola,
and Samfya. These districts are part of the ten Roll-Back
Malaria (RBM) monitoring sentinel surveillance sites.
They were chosen based on geographical distribution and
the malaria incidence strata. In each district, three study
sites (health facility) were purposively sampled. Three
facilities from each district were selected and assigned one
of each type of malaria diagnosis (microscopy, rapid diagnostic tests or clinical) depending on current practice. The
existing microscopy services at some health facility were
maintained while RDTs were introduced in facilities with
no diagnostic services. This brought the total of facilities
under investigation to 18 (3 facilities from each district).

After the sites were selected, initial orientation of health

staff was conducted on data capturing, record keeping and
the need to observe and record review cases. The person
in-charge of each facility was responsible for supervising
the in-house data collection process. Further, within each
district, there is a malaria information officer who provided weekly supervisory visits to three facilities under
their jurisdiction. The national team was also responsible
for close supervision, on a monthly basis to ensure that
supplies were adequate and that record keeping was being
adhered to. During these visits, data entry was scrutinized
to ensure that register scores matched tally sheets. Members of staff were also interviewed on how the survey was
proceeding. The three levels of supervision helped to
ensure that data collection instructions were strictly followed.
Data entry was undertaken in a Microsoft Access program
based data base through customized data entry screens
with in-built range and consistency checks. The data was
entered by independent data entry clerks, with completed
data files compared for data-entry errors. All data entry
and management was undertaken at the National Malaria
Control Centre (NMCC). Data entry was closely supervised with any summaries generated from the database
compared with hand-tallied summaries to ensure consist-

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ency. Data collection proceeded from February through

November 2005.
Effectiveness indicators
The clinical impact of AL is usually considered in terms of:
(i) prevention of treatment failure associated with SP, and
(ii) prevention of aggravation from simple malaria to
severe malaria. In line with these attributes, the study
defined two indicators of effectiveness. The first indicator
considered the number of cases of malaria successfully
treated. This indicator assumes that the main aim of treatment policy is to maximize the number of cases successfully treated from available resources. In the study design,
successful treatment was defined as patient showing negative parasitaemia after treatment with AL. This measure
was computed from field data on efficacy, compliance
and clinical success from a paired survey on the same
patient population. A simple model was constructed to
predict the number of successfully treated cases under the
two treatment regimens.

The second indicator of clinical effectiveness was the proportion of malaria cases proceeding to severe malaria,
which essentially indicates the degree to which AL prevents disease aggravation [17]. Severe malaria is also a
good predictor of malaria mortality. According to case
management guidelines, severe malaria is identified by
any of several typical clinical syndromes including: high
fever with respiratory distress (abnormally fast breathing),
convulsions, hyperparasitaemia (where microscopy is
available), anaemic symptoms and neurological disturbances. This indicator of effectiveness was mirrored in as
health outcome data namely, number of clinical severe
malaria cases as a proportion of uncomplicated malaria
cases. Severe malaria cases data was collected also from
the facility registers from all the 18 facilities under study
during the entire study period.
Costing
The costing was done from a providers' perspective. (i.e.
the public health system). This means that only costs
borne by the health facilities during the provision of
malaria treatment services have been considered. Cost elements included were drugs, personnel, medical examination, materials, administrative and equipment overheads,
and building space. Except for drug and medical examination costs, all other costs were treated as overheads with
the malaria-related cost derived using the direct attribution method (i.e. relative malaria prevalence). After
obtaining cost attributed to malaria, average total cost per
malaria case was calculated as the total malaria related
costs divided by total number of malaria cases. Cost data
were gathered from both secondary and primary sources.

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A questionnaire was designed and used to capture data

from health facilities on quantities and prices of various
cost inputs including capital assets, equipment, materials
and personnel. Capital assets typically included building
space in meters, motorbikes, motor vehicles and furniture
such as chairs, tables and cabinets. Facilities reported only
basic equipment such as microscope, stethoscope, sphygmomanometer, thermometer, laboratory equipment,
refrigerator, cold chain, weighing scales. Purchase prices
obtained from health facilities were used to derive discounted annual capital costs. Equipment and motor vehicles were annualized using a discount rate of 3% and
lifespan of five years, while buildings were given a life
span of 30 years at the same discount rate. The 3% discount rate has been used extensively in the literature [18].
Data on the cost per square meter of health facility was
provided by the Physical Planning Division of the Ministry of Health. Once the costing was done, allocation of
costs attributable to malaria was based on total utilization
of OPD resources for other diseases as a denominator and
total malaria utilization as the numerator. It has been
assumed that 40% of OPD cases are due to malaria.
Labour costs were computed using the time spent by each
staff cadre in treating a case of malaria or suspected
malaria. Staff time was multiplied by pro rata earnings
(salary plus standard allowances) for each staff category
involved in treating malaria. Salary data was gathered
from respective staff members. All cost estimates from
past years was converted to 2005 prices using official
exchange rate US$1 = ZMK3,500. The costs were computed using standard costing approaches in economic
evaluation [18]. Costs of switching to other forms of treatment during a single illness episode have not been
included in this costing.
Cost of second-line treatment
In addition, this study required estimating the cost of
treating patients with complicated or mildly severe
malaria. An investigation of actual practice for patients
not cured within the 28-day period revealed the following
scenarios: (i) three waves of treatment are administered to
patients failing first line treatment (ii) returning patients
receive repeated first-line treatment regardless of parasitological status, (iii) efficacy of repeated first-line unknown,
and (iv) after failure of second attempt, returning patients
are either referred further or treated with second-line treatment. This implies that after repeated first-line fails,
patients either develop complicated malaria, get cured,
seek alternative providers (including home remedies) or
are treated for something else. With the exception of the
first, the potential effects of these possibilities in an incremental framework are held constant in this study. This is
a strong assumption. According to the data, 4.7% of AL

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recipients and 48.1% of SP recipients were treated for

complicated malaria. Further, it was assumed that the efficacy of second-line treatment is the same regardless of
first-line treatment given. These scenarios were constructed using data obtained from malaria facility registers, field surveys and interviews with health workers.
The methodology of costing described above was used to
obtain the average cost of treating an episode of complicated malaria with second line treatment. However, complicated malaria is treated at various levels within the
health care system, with each of these levels having different costs. Patients with complicated malaria present
themselves at four facility options namely health centre
outpatient, health centre inpatient, hospital outpatient
and hospital admission. Data on the fraction of patients
seeking severe malaria treatment at each of these facilities
as well as estimated treatment costs for complicated
malaria treatment were obtained from two recent surveys
[19,20]. The cost per case of severe malaria treated was calculated using as a weighted average of the cost per episode
at four different levels.
Methods of analysis
The cost-effectiveness model used considers three important elements. First, the study reports on estimates of the
treatment cost per episode. Treatment cost measures and
values the resource inputs that are required to produce a
malaria therapy. Second, the study estimates the average
cost-effectiveness ratio (ACER). The ACER estimates the
cost per each case of malaria success fully treated. Formally, this is defined as the total cost of treating all cases
somehow diagnosed as malaria divided by the total
number of cases considered having been cured within the
28-day period. This means that, holding cost constant, a
therapy with the highest number of successful treatment
outcomes will have a lower ACER. The lower the ACER the
more preferred the therapy.

The formula of the average cost-effectiveness ratios is as

follows,

ACERAL =

Estimated total cost of treatment ( AL)

,
Effectiveness (AL)

ACERSP =

Estimated total cost of treatment (SP)

.
Effectiveness (SP)

Finally, when thinking about a new alternative drug (AL),

which would be mutually exclusive with an existing drug
(SP), the amount of resources available becomes an
important consideration. An appropriate framework for
addressing this question is the incremental cost effectiveness ratio (ICER). The ICER measures the additional cost
that is required in order to achieve a superior health effect

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over the baseline. For instance, a switch from SP to AL has

meant that a more expensive drug is being used to compensate for the inferior health benefits of SP. Thus, the
extra health benefits of AL come with an extra cost. Intuitively, the ICER is defined as the additional cost of treatment with AL divided by the additional health effects of
AL. This analysis begs the question of whether the extra
cost per additional benefit generated is worth paying for
or not. Although this question is germane to a different
form of economic evaluation known as cost-benefit analysis, or may be even to politics [18,21]. The idea is to compare these results with similar studies in similar countries
for similar studies and also to refer to ICER thresholds that
been customarily applied in cost-effectiveness studies.
The formula for calculating the ICER was defined as follows,
ICERAL,SP =

Expected total cost of treatment (ACT) - Expected

d total cost of treatment (SP)
Expected effectiveness (ACT) - Expected effectiveness (SP)

Ethical considerations
This study was approved by the Ethics Committee at the
Tropical Disease Research Centre (TDRC). The study was
also cleared by the Director General's Office of the Central
Board of Health. Further, local support was sought from
the District Director of Health in each district and also the
in-charge of the given facilities. Such consensus led to
high cooperation in terms of the study operation and
logistics. No names of patients were divulged during data
analysis, only age and sex characteristics were shown. As
the study data gathering process was restricted to malaria
registers at facilities, with no contact with patients or
patient names, no major ethical issues arose.

Results
Cost of treatment
Table 1 presents estimates of the average cost of treating
an episode of uncomplicated malaria with SP compared
with AL. Costs included drugs, personnel, medical examination, and administrative and equipment overheads and
capital cost. Data for estimating costs was obtained from
facilities. It is shown that the cost of treatment with SP
(US$6.19) is far less than treatment with AL (US$7.34),
implying that AL will increase the overall cost malaria
treatment in Zambia. It can also be seen that the introduction of the more expensive AL changes the cost structure
of the malaria programme by increasing the drug component of malaria budget of Ministry of Health. The average
cost per case treated is almost 20% higher with AL. It can
also be seen that the cost structure has changed drastically
with the drug component of total direct health system
costs of treating malaria having gone up six fold.

These estimates compare very well with comparable estimates from a Tanzanian study in which the cost of SP and

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Table 1: Average costs of treating an episode of uncomplicated malaria: SP and AL

Cost item

1. Drugs
2. Diagnostics (medical examination)
3. Personnel
4. Administration and other overheads compliance
5. Capital (equipment and buildings)
6. Average Total cost per patient treated

AL were US$5.09 and US$5.96, respectively [22]. However, if converted to year 2000 international dollars, these
estimates are nearly 50% higher than the estimates
derived from the World Health Organisation cost-effectiveness model known as the WHO-CHOICE. The WHOCHOICE cost estimate per episode was $5.97 in 2000
international (i.e. purchasing power parity) dollars
excluding drugs and diagnostic components [23].
Cost-effectiveness analyses
Using costs and effects estimated above, the cost-effectiveness ratios were estimated as depicted in table 2. According to the cost-effectiveness framework described earlier,
the cost per case successfully treated as well as the incremental cost per each extra case successfully cured, with AL
in relation to SP, were estimated.
Cost-effectiveness ratio for cost per case successfully
treated
The first element of the cost-effectiveness analysis was the
average cost per case successfully treated patient (ACER):
SP versus AL. A simple model illustrated in Table 2 has
been used to derive treatment success and the cost per case
successfully treated. This model uses input data on efficacy, compliance and treatment success without full compliance to estimate the average cost-effectiveness ratio for
SP and AL. The input data has been gathered from two
parallel surveys on drug efficacy and compliance as indicated earlier.

The model begins with a cohort of 55,509 patients presenting for treatment with SP and AL. The choice of
55,509 was a convenience as this was the total number of
malaria cases recorded in 2005. As indicated above, using
in vivo data on drug efficacy and compliance from the
same population the curative success rate for both SP and
AL is estimated. In particular, the model estimates the
number of cases successfully treated from an equal cohort
of 55,509 of patients under the two regimens, SP and AL,

AL

SP

Cost (US$)

percentage

Cost (US$)

Percentage

1.33
4.25
0.84
0.54
0.38
7.34

18
58
12
7
5
100

0.18
4.25
0.84
0.54
0.38
6.19

3
69
14
9
6
100

using the parameters contained in Table 2, according to

the formula:
Number of cases successfully treated = R1* [(R2*R3) + (1
- R3)R4]
The first component on the left hand side measures the
number of cases successfully after full compliance, while
the second term measures the number of patients who are
cured from the proportion that is assumed not to fully
comply with the treatment dosage.
In this model, it assumed that 50% of patients who do not
comply with the complete dosage of AL are still cured. A
recent study assumed that 45% of non-complying
patients using AL in similar settings still get cured [24].
Interviews with malaria case management experts at the
National Malaria Centre also suggest that this is a realistic
assumption.
As was shown in Table 1, the average cost per case treated
(i.e. given anti-malarial) was about US$7.34 and US$6.19
for AL and SP, respectively. The study also estimates that
malaria expenditure per capita on first-line treatment is
higher if AL is used. This finding confirms unequivocally
that the decision to adopt AL as the first-line drug for
malaria treatment will require additional financing for
malaria case management, at least in the short term (28day window).
However, the average cost-effectiveness ratio, defined as
the total treatment cost divided by the total number of
cases successfully treated (i.e. cost per cured case), has
been estimated at US$8.57 and US$10.65 for AL and SP
respectively, as shown in Table 2. On this account, treatment with AL is more cost-effective than SP. This finding
clearly indicates that as much as treatment with SP may
appear cheaper in terms of budgetary outlays, it is shown
that as the cost per the relevant output produced (cases

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Table 2: Estimated number of cases successfully treated and average cost-effectiveness

Effects/cost
1. Patients starting treatment (2005)
2. Efficacy
3. Patient Compliance
4. Treatment successful despite less than full compliance
5. Number of cases successfully treated*
6. Total expenditure on treating malaria
7. Average Cost-effectiveness Ratio (average cost per case cured)
8. Incremental cost per case successfully treated

AL

SP

55509
98.2%
75.1%
50%
47560
406370.69
$8.57
4.10

55509
68.4%
85.0%
0
32273
343743.64
$10.65
-

Items in Rows 5, 6, 7 and 8 estimated from formula in section 3. Input data on efficacy and compliance obtained from surveys [12-16].

cured) works out lower with AL. A crucial implication of

this result is that for a given amount of resources (fixed
case management budget), AL produces more cured
patients while the use of SP would have given us more
dosages dispensed but with proportionately less cured
cases. According to the rule of thumb in cost-effectiveness
analysis, the answer to the question of whether AL is costeffective is in the affirmative.
Incremental cost-effectiveness ratio (ICER)
The demonstrated superior effectiveness of AL has come at
an additional price. This extra or incremental cost of producing one extra successful cure of an episode of malaria
is known as the incremental cost-effectiveness ratio. Referring to the formula presented earlier, the incremental costeffectiveness ratio of AL estimated in this study is
US$4.10. This is the amount that it costs to achieve one
extra successfully-treated case using AL in relation to SP.
This estimate of incremental cost-effectiveness is within
an order of magnitude of estimates from similar studies. A
study in Tanzania estimated that the incremental cost of
changing malaria first-line treatment from CQ to SP was
US$0.20 [25].
Incremental cost-effectiveness of AL including second line
treatment
An incremental cost-effectiveness analysis of first line
treatment might be considered incomplete particularly in
the context of AL whose main impact, in this context, lies
in reducing the cost of advanced malaria. ACTs are particularly favoured for early and more vigorous action against
the parasite thereby reducing the probability of disease
aggravation, mortality and recurrence of malaria. This section presents a simplified model that estimates the incremental cost-effectiveness ratio of using AL as first line
treatment versus a regimen that uses SP for first line. In
both cases, quinine is used as second line treatment of
complicated or severe malaria. Based on data from all

sites, the weighted average cost of severe malaria treatment was worked out to be US$ 16.32.
Results of the incremental cost-effectiveness ratio including the costs of repeated first-line and second-line treatments are constructed in table 3.
AL is dominant indicating that there are resource savings
from reduced second line treatment that are associated
with AL. The data shows that these savings emanate from
comparatively fewer patients treated more than once with
AL and even fewer patients treated for complicated
malaria. These phenomena are known from a public
health point of view but have not really been demonstrated in an economic framework. In this broader perspective, the case for AL is even more persuasive.

Discussion
This study has revealed that adopting AL over SP raises the
total cost of treatment thereby requiring substantial
investments into the national malaria case management.
However, the study has also demonstrated that AL produces much better health outcomes in terms of curative
success and reduction in the cost of complicated or severe
malaria treatment. Despite its higher cost per complete
dosage, the cost per case treated successfully is much
lower with AL on account of the effectiveness of AL in
eradicating malaria infection in patients within the 28-day
period. The cost-effectiveness ratio calculated in this study
compare very well with similar findings from similar setting [22]. This reinforces the superiority of AL over SP
from a cost-effectiveness perspective. In addition, it has
been shown that a reduction in the burden of severe
malaria reduces the need for hospital care. This leads to
cost savings on reduced hospitalization. The health benefits of AL are likely to offer a considerable opportunity for
reducing demands on scarce human resources given that
malaria accounts for a highest proportion of visits and
hospital admissions.

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Table 3: Incremental cost-effectiveness of artemether-lumefantrine including second line treatment

1. Total patients
2. First wave first-line, US$a
3. Second wave first-line, US$b
4. Second line treatment, US$c
5. Incremental cost, US$
6. ACER including second line treatment, US$
7. ICER including second line treatment, US$

AL

SP

55,509
407,436.06
58,263.36
6,088.60
-176,486.97
9.92
-11.52

55,509
343,600.71
143,968.70
182,575.57
20.78
-

(a) All patients receive first wave first-line

(b) 14.7% of AL and 41.9% of SP recipients fail first-line and receive repeated dosage
(c) cost of second line treatment is us$16.32

Further, a simple model applied in this study suggests that

the incremental cost effectiveness ratio of AL falls well
within customary incremental cost thresholds. In fact, by
the recent standards of WHO, AL would fall within the
category classified as highly cost-effective interventions. A
policy decision is needed to evaluate whether this incremental cost-effectiveness ratio of US$4.10 is worth paying
for. A natural perspective to take in evaluating this figure
is to refer to the WHO Commission on Macroeconomics
and Health criteria on incremental cost-effectiveness
ratios (ICER) of US$25 or a nation's per capita Gross
National Product [26,27].
The reduction in treatment failure and the prevalence of
severe malaria in a cohort of patients that is associated
with AL has naturally raised issues about causality. Using
data obtained from facilities on cases of severe malaria
cases recorded, it is indicated that a reduction of up to
91% was observed. This analysis excludes the confounding effects of reporting bias. If there is greater systematic
under-reporting of severe malaria in population during
the post-intervention period (in 2005) than was the case
previously, then these results are likely to be biased
upwards. The contribution of AL to this impact is still contentious. Malaria experts in Zambia have expressed an
opinion that AL has contributed to a reduction in malaria
morbidity. Collaborating data from an independent study
point to a strong correlation between AL use and reduction in severe malaria admissions. In particular, at the
Macha Malaria Institute in the southern province of Zambian, researchers show that cases of severe malaria in children had declined to virtually zero. Intrigued by dramatic
reduction in malaria cases after the introduction of ACTs,
the study team at Macha began to collect data on children
with malaria.
"Malaria prevalence surveys are showing less than 5% parasite
positivity rate by thick smear compared to 50% or more in previous years by this time in the rainy season. Interestingly, these
surveys are showing that there is no decline in the number of
anophelines."

Interviews with malaria experts introduced a useful albeit

subjective dimension of explaining the contribution of AL
to malaria morbidity and mortality trends. Opinions from
field researchers in Macha suggest a strong link between
AL and the decline in malaria morbidity and mortality.
"Thus, it seems to me, that while there should be no competition
between the various interventions (we all need each other), that
the evidence is much more strongly in favour of effective firstline therapy with ACTs than it is with use of ITNs or IRS programmes, if we want to decrease malaria morbidity and mortality" [28].
"Admissions to the children's ward for malaria are still very
rare so far this year as compared to previous years. I we have
probably admitted only 14 cases between November 2005 and
February 2006. Out of these, four were severe malaria cases. In
the 20012 season, Macha hospital admitted 1,517 children
with severe malaria and for a similar period in 20045, we
recorded 157. Malaria case fatality rates decreased from 52 to
7."
The Macha Malaria Research Institute team believes that
eliminating malaria among the population though effective case management has helped reduce the transmission
rate within the population. Importantly, it should also be
borne in mind that in the villages around Macha, there
has been no in-door residual spraying (IRS) activities
while the insecticide treated net (ITN) coverage is very low
(assumed by Macha malaria institute staff to be at about
46%). Although these claims of AL effectiveness appear
credible to clinicians and many field workers, they can
only be validated by systematically gathered data. In addition, it remains to be seen if these observations are only
short-term changes or they can be sustained over a longer
period.
This study conducted interviews with health staff and
community members through focus group discussions at
three of the six sites (Chingola, Kabwe and Samfya). The
information gathered indicated that public perceptions
about the curative advantages of AL over previous drugs

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have seemingly helped to boost demand for public health

care and helping to initiate early treatment. Though this
information is anecdotal, the views from both health and
community workers regarding the effectiveness of AL were
unanimous. A community worker at a focus group discussion in Kabwe giving her views on the positive influence
of an effective drug on choice of care:
"The experience with patients who have been put on artemether-lumefantrine has shown that many patients are
responding well to this drug and seem to prefer it. Even patients
that used to go to witch doctors are now reporting to public facilities for treatment. In the past when people did not get cured
with a single visit to a clinic, they would turn to a traditional
healer."
Further, the impact of AL on the scale estimated in this
study is in line with findings from at least two surveys that
have evaluated the efficacy of AL in Africa as well as
another independent study conducted in Zambia [29-33].
Finally, it is important to remember that the potential
contribution of malaria prevention interventions such as
ITNs and IRS on observed the cost-effectiveness of AL is
likely to be very limited because of their low coverage.
Many malaria experts have considered that for ITN and
IRS interventions to make a substantial impact on malaria
incidence, population coverage should be at least 50%.
Sensitivity analysis
Sensitivity analysis was performed to show whether the
parameters used in estimating cost-effectiveness ratios are
robust to some degree of uncertainty. Importantly, this
analysis allows an evaluation of the potential effect of
misdiagnosis in the context of the design of this study. For
several reasons, malaria misdiagnosis is perhaps a rule
rather than an exception in many endemic countries.
Assuming that up to 60% of cases recorded and treated as
malaria might not have been true malaria, the cost and
cost-effectiveness implications are considered in table 4.
Basically, both the ACER and the ICER of AL rise significantly, indicating that presumptive treatment of fevers
reduces the attractiveness (i.e. cost-effectiveness) of AL in
relation to SP. The cost-effectiveness implications of alterations to the values of other parameters applied in estimating ACER and ICER are shown in table 4. The main
conclusions remain as before, although the ICER increases
but still remains in the same order of magnitude. Thus,
the results of this sensitivity analysis suggest that the key
cost-effectiveness results remain robust to plausible variations of the main assumptions used in the model.
Limitations and recommendations for further research
A number of limitations which raise some caveats of this
study can be mentioned. One limitation of the study is
that it did not consider a societal perspective of costing. It

http://www.malariajournal.com/content/6/1/21

would be of great interest to see how resilient the costeffectiveness conclusions derived from this perspective
are, to the inclusion of societal, or at least patient, costs.
Second, the survey conducted in six of the sentinel sites
that have witnessed anti-malaria activities for some time,
the results may not be generalized to the entire population. It would be interesting to see what future work in
other areas could suggest. Third, the study adopted a definition of malaria imposed by actual behaviour of health
workers. This may have interfered with the estimated costeffectiveness ratios in one way or the other. It would be
important to study the effects of adherence to diagnostic
results especially in the case of adult patients. Future work
could focus on this important issue.
Further, this study considered only treatment success
within a 28-day period. Cases that were reported after this
period were considered to be new infections. In addition,
it remains to be seen if the impact observed with the introduction of AL will be sustained over a long time. Since
resistance and treatment failure are dynamic concepts, the
cost-effectiveness analysis of introducing a new treatment
such as ACTs should not be done from a static point of
view but rather from a dynamic perspective.

Conclusion
This study is one of pioneering studies investigating the
cost-effectiveness of AL in a real African health system setting. Concerns over the high cost of ACTs relative to SP
and chloroquine have dominated the policy debate
around the introduction of ACTs in Zambia and other
low-income countries. Many commentators have questioned both the affordability and sustainability of ACTs in
a resource-poor and weak health system setting such as
Zambia's. A relevant question to ask, however, is whether
the extra cost of AL is worth the extra health benefits that
AL confers on patients and the health system in general.
Accordingly, this study has performed a cost-effectiveness
analysis to provide guidance on the key issues arising
from changing malaria treatment policy in the face of drug
resistance to other anti-malarials. By comparing both the
health effects and cost of AL against SP, a cost-effectiveness framework helps us to inform this debate through a
careful assessment of both costs or financial outlays and
health benefits.
As the debate on affordability of AL continues, this study
shows that substantial extra resources will be required to
sustain the scale up of treatment with AL as well for a supporting prevention strategy. Cost-effectiveness analysis
should not be confused with costing analysis or cost-benefit analysis. While it is acknowledged that implementing
national ACT program will require considerable resources
in the short-term, the thrust of this study demonstrates
that the health gains (as defined by treatment success)

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Table 4: Sensitivity of CEA results to parameter alterations

Parameter alterations

Effect on ACER and ICER

CEA conclusion

Discount rate in estimating capital costs is 10%

instead of 3%
AL costs 10% more than estimated

No effect as cost of both AL and SP rise by

same margin
ACER increases to US$8.67 ICER increases to
US$4.57
ACER increases to US$8.75 ICER to US$4.81

Unchanged

AL costs 15% more than estimated

AL costs 50% more than estimated
Compliance of AL is lower at 65%
Efficacy of AL is lower at 90%
Efficacy of AL is lower at 80%
Proportion of patients seeking second line
treatment is 4.7% in both AL and SP
Diagnosis of malaria is poor and 60% of cases
treated are actually non-malaria cases for both
AL and SP

Proportion of patients progressing to severe

malaria is same at 4.7% for both AL and SP

ACER and ICER of AL increase to US$9.29 and

US$6.47
ACER increases to US$9.02 ICER increases to
US$4.95
ACER increases to US$9.17 ICER to US$5.25
ACER increases to US$10.12 ICER increases to
US$7.99
ICER of AL is now US$3.10
Incremental cost will remain the same but the
number of cases successfully treated will drop.
The cost per cases successfully treated rises
proportionately to US$ 21.29 and US$26.62
for AL and SP respectively. ICER rises from
US$4.10 to US$10.25.
ACER of SP decreases substantially from
US$20.78 to $15.75 but still higher in relation
to AL. ICER increases from US$-11.52 to US$0.94.

from every dollar spent are significantly greater if AL is

used rather than SP. This is a different issue from stating
that AL is affordable. In fact it was shown that for a limited
budget, SP will provide more dosages, though with much
less positive effect.
The study points out that case management alone is insufficient to guarantee a sustained reduction in morbidity
and mortality. While AL is cost-effective, it is not a subject
for transmission control through bed nets and residual
spraying. A combination of prevention to halt malaria
transmission and the use of an effective drug for prompt
treatment of cases would confer substantial economic and
health gains. In conclusion, this analysis strongly suggests
the decision to adopt AL is clearly justifiable on both economic and public health grounds.

Competing interests
The authors would like to acknowledge that Norvatis
Pharmaceuticals provided the funding for this study
through the Zambian Ministry of Health. However, none
of the authors works for, or represents in any way, Norvatis Pharmaceuticals.

Authors' contributions
PC participated in developing the research protocol, field
work supervision, data analysis and drafting this manu-

Unchanged in terms of ACER but ICER

increases by 18%
Unchanged in terms of ACER but ICER
increases by nearly 20%
Unchanged in terms of ACER but ICER
increases by 27%
Unchanged but ICER increases by
Unchanged but ICER increases by nearly 30%
Unchanged but ICER increases by 95%
The cost of additional successfully treated case
is US$3.10
Decision still in favour of AL but the costs are
much higher with ICER more-than doubling

ACER and ICER conclusions remain same

script. FM was involved in designing data collection

instruments, field supervision, data analysis and drafting
this manuscript. BMC was involved in designing the
research protocol, data collection, data analysis and drafting this manuscript. PB was involved in research protocol
development, data collection, supervision of field work
and editing this manuscript. MH was involved in research
protocol development, data collection, supervision of
field work and editing this manuscript. NS participated in
designing the research protocol, data collection, supervision of field work, data analysis and drafting this manuscript. TO reviewed the methodology, undertook some
field visits and participated in the drafting of the manuscript.

Acknowledgements
Special thanks are due to all the six District Health Management Teams
who rendered logistical and personnel support to the study team during the
entire duration of the data collection exercise. The team is also sincerely
thankful to the various staff at the Ministry of Heath, the Central Board of
Health and the National Malaria Control Centre for the multifaceted support they rendered to this study. The team would like to gratefully
acknowledge the technical support rendered to the study team by the
WHO-AFRO through the National Malaria Control Centre (NMCC). A
final call of gratitude is due to all the research assistants for their dedication
to this work during data collection, entry and cleaning. The usual disclaimers apply.

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