The financial and clinical implications of adult malaria diagnosis using microscopy in Kenya

The financial and clinical implications of adult malaria diagnosis

using microscopy in Kenya

D. Zurovac1,2, B. A. Larson3,4,5, W. Akhwale6 and R. W. Snow1,2

1 Malaria Public Health and Epidemiology Group, Kenya Medical Research Institute/Wellcome Trust Research Laboratories, Nairobi,Kenya

2 Centre for Tropical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK3 Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya4 Center for International Health and Development, Boston University, Boston, MA, USA5 Department of Agricultural and Resource Economics, University of Connecticut, Storrs, CT, USA6 Division of Malaria Control, Ministry of Health, Nairobi, Kenya

Summary objective A recent observational study undertaken at 17 health facilities with microscopy in Kenya

revealed that potential benefits of malaria microscopy are not realized because of irrational clinical

practices and the low accuracy of routine microscopy. Using these data, we modelled financial and

clinical implications of revised clinical practices and improved accuracy of malaria microscopy among

adult outpatients under the artemether–lumefantrine (AL) treatment policy for uncomplicated malaria in

Kenya.

methods The cost of AL, antibiotics and malaria microscopy and the expected number of malaria

diagnosis errors were estimated per 1000 adult outpatients presenting at a facility with microscopy

under three scenarios: (1) current clinical practice and accuracy of microscopy (option A), (2) revised

clinical practice with current accuracy of microscopy (option B) and (3) revised clinical practice with

improved accuracy of microscopy (option C). Revised clinical practice was defined as performing a

blood slide for all febrile adults and prescribing antimalarial treatment only for positive results.

Improved accuracy of routine microscopy was defined as 90% sensitivity and specificity. In the sensi-

tivity analysis, the implications of changes in the cost of drugs and malaria microscopy and changes in

background malaria prevalence were examined for each option.

results The costs of AL, antibiotics and malaria microscopy decreased from $2154 under option A to

$1254 under option B and $892 under option C. Of the cost savings from option C, 72% was from

changes in clinical practice, while 28% was from improvements in the accuracy of microscopy. Com-

pared with 638 malaria overdiagnosis errors per 1000 adults under option A, 375 and 548 fewer

overdiagnosis errors were estimated, respectively, under options B and C. At the same time, the number

of missed malaria diagnoses remained generally low under all options. Sensitivity analysis showed that

both options B and C are robust to a wide range of assumptions on the costs of drugs, costs of blood

slides and malaria prevalence.

conclusions Even with the imperfect microscopy conditions at Kenyan facilities, implementation of

revised clinical practice (option B) would substantially reduce the costs and errors from malaria over-

diagnosis. Additional interventions to improve the accuracy of microscopy (option C) can achieve

further benefits; however, improved microscopy in the absence of revised clinical practice is unlikely to

generate significant cost savings. Revision of guidelines to state explicitly age-specific indications for the

use and interpretation of malaria microscopy is urgently needed. Further prospective studies are required

to evaluate the effectiveness and costs of interventions to improve clinical practice and the accuracy of

malaria microscopy.

keywords malaria, microscopy, cost, diagnosis errors, clinical practice

Tropical Medicine and International Health doi:10.1111/j.1365-3156.2006.01674.x

volume 11 no 8 pp 1185–1194 august 2006

ª 2006 Blackwell Publishing Ltd 1185

Introduction

Current malaria diagnostic and clinical practices in sub-

Saharan Africa result in massive overdiagnosis and over-

treatment of malaria (Amexo et al. 2004; Reyburn et al.

2004; Zurovac et al. 2006). Higher risks of malaria

infection, disease, and death in non-immune children

below 5 years of age (Trape & Rogier 1996; Snow &

Marsh 1998; Snow et al. 2003a) support diagnostic

approaches to treat presumptively all febrile children in

most malaria endemic areas. However, presumptive treat-

ment of older children and adults, which accounts for a

major age-specific share of antimalarial drugs (Snow et al.

2003b), will become less acceptable when significantly

more expensive Artemisinin-based combination therapies

(ACTs) are adopted and implemented as the recommended

first-line therapies for uncomplicated malaria (WHO 2001;

Malenga et al. 2005). Malaria microscopy has been tradi-

tionally seen as one of the potential solutions to increase

diagnostic specificity and overcome the problem of malaria

overdiagnosis (WHO 2000).

However, during our earlier observational study in

Kenya, we demonstrated that potential benefits of micr-

oscopy are not realized among older children and adults

for three main reasons (Zurovac et al. 2006). First, blood

slides were frequently performed for patients without

fever. Secondly, the accuracy of routine microscopy was

low with errors tending towards overreporting of positive

slide results. Thirdly, the results of the routine negative

blood slides, which were correct 92% of the time, were

ignored, and the majority of patients with negative blood

slides were prescribed antimalarials.

As of 2006, Kenya will implement a specific ACT,

artemether–lumefantrine (AL), as the recommended first-

line therapy for uncomplicated malaria. The continuation

of current clinical and laboratory practices with AL will

inevitably waste precious resources. To support imple-

mentation of new Kenyan AL policy, this article analyses

the financial and clinical implications of improving the

accuracy of malaria microscopy and changing common

clinical practices among adult outpatients presenting to a

typical health facility with microscopy.

To undertake this analysis, we used data on adults

(‡15 years) from a recent study evaluating outpatient

malaria case management in patients above 5 years of age

at 17 health facilities with functional microscopy in two

Kenyan districts (Zurovac et al. 2006). The small number

of observations in older children (5–14 years) in our earlier

study did not allow a detailed analysis for this age group.

As adults accounted for 79% of all malaria treatments in

our previous study, demonstrating the financial and clinical

utility of revising clinical practice for adults is an important

first step before considering appropriate policy for older

children. This analysis also provides information that is

directly relevant to the process of revising the National

Guidelines for Diagnosis, Treatment and Prevention of

Malaria for Health Workers in Kenya (MoH 1998).

Methods

Definitions of policy options

We organize our analysis as the evaluation of three policy

options:

• Option A is the continuation of current clinical

practice in an era of AL. This option provides the

benchmark from which other options are evaluated.

• Option B requires a change in clinical practice so that

(i) blood slides are performed for all febrile adults and

no blood slides are performed for non-febrile adults

and (ii) all adults with routine blood slides reported as

negative under current practices are not prescribed AL

and all adults with routine positive blood slides are

prescribed AL.

• Option C is option B combined with a substantial

improvement in the accuracy of malaria microscopy

(from 66.7% sensitivity and 64.7% specificity to 90%

for both).

We do not argue that option C is feasible to implement

in Kenya in the near future, but it provides an alternative

benchmark for understanding the outcomes associated

with options A and B. Implementing option B would

clearly involve interventions to implement revised clinical

practices, while option C would involve interventions to

revise clinical practice and to realize improvements in the

accuracy of routine microscopy. The costs of such inter-

ventions are not included in this analysis because their

content, effectiveness and costs are essentially unknown.

However, the incremental changes in costs and risks of

moving from option A to option B and option C show the

maximum incremental benefits of such investment.

Determination of initial model parameter values

Results from our earlier observational study are summar-

ized as four adult treatment branches in Figure 1, where

branch 1 is for outpatients presenting without a fever who

do not have a blood slide performed; branch 2 is for

outpatients presenting without a fever who have a blood

slide performed; branch 3 is for outpatients presenting with

a fever who do not have a blood slide performed and branch

4 is for outpatients presenting with a fever who have a blood

slide performed. We use the basic information provided in

Tropical Medicine and International Health volume 11 no 8 pp 1185–1194 august 2006

D. Zurovac et al. Financial and clinical implications of malaria microscopy

1186 ª 2006 Blackwell Publishing Ltd

https://www.researchgate.net/publication/7225085_Microscopy_and_outpatient_malaria_case_management_among_older_children_and_adults_in_Kenya?el=1_x_8&enrichId=rgreq-a9ff61f1-ec83-4f5c-85c8-e653926e2867&enrichSource=Y292ZXJQYWdlOzY4ODMzMDI7QVM6MTQ5MjE4NTU5Nzk1MjAwQDE0MTI1ODc4ODU5MzE=


Figure 1 to develop the initial model of existing clinical

practice (option A). Figure 2 shows the revision of clinical

practice proposed as option B. Figure 2 also summarizes the

revision of clinical practice envisioned as option C.

Three assumptions for comparing options A, B and C

need to be mentioned here. First, we allow the same

percentage of non-febrile adults without a blood slide to

be prescribed AL (k1 ¼ 0.10) for options B and C as

option A. We do not suggest that this is good clinical

practice, but we acknowledge that some non-febrile

adults are likely to be prescribed AL if either option B or

option C was implemented. Secondly, adults who would

fall into branch 2 for option A are moved to branch 1

for options B and C. Because of this shift, we assume

Adult Outpatients (n)†

% BS Not Done(1–g) = 0.476

% Without Fever(1–p ) = 0.22

% BS Doneg = 0.542

% Rx with ABfor all patientsin Branch 1m

1 = 0.87

% BS Negative(1–spr

2R) = 0.697

% BS Positivespr

2R

= 0.303

% Rx with ALb

2 = 0.652

% Rx with ALa

2 = 1.0

“Branch 1” “Branch 2”

% BS Not Done(1–h) = 0.229

% With Feverp = 0.78

% BS Doneh = 0.771

% Rx with ALl

3 = 0.49

% BS Negative(1–spr

4R) = 0.609

% BS Positivespr

4R

= 0.391

% Rx with ALb

4 = 0.835

% Rx with ALa

4 = 0.957

“Branch 3”“Branch 4”

% Rx with ALl

1 = 0.10


2 = 0.64

% Rx with ABfor all patients in Branch 3m

3 = 0.47


4 = 0.50

Figure 1 The clinical process for adultoutpatients for option A*. *In each box, the

variable is defined, notation for the variable

is specified and the basic values obtained

from Zurovac et al. (2006) are provided.All percentages are reported in decimal

format (i.e. 22% is denoted as 0.22).

�The sample refers to 286 adult outpatients

‡15 years obtained from Zurovac et al.(2006). BS, blood slide; Rx, treatment; AL,

artemether–lumefantrine; AB, antibiotic.

Adult Outpatients (n)

% BS Not Done(1–g) = 1.0

% Without Fever(1–p ) = 0.22

% BS Doneg = 0.0


1 = 0.87


% BS Not Done(1–h) = 0.0

% BS Doneh = 1.0

% BS NegativeOption B: (1–spr

4R) = 0.609

Option C: (1–spr4

R) = 0.802

% BS PositiveOption B: spr

4R

= 0.391

Option C: spr4R

= 0.198

% Rx with ALb

4 = 0.0


% Rx with ALl

1 = 0.10


4 = 0.50

% Rx with ALa

4 = 1.0

% With Feverp = 0.78

Figure 2 The clinical process for adult

outpatients for options B and C with nota-

tion and parameter values*. *In each box,the variable is defined, the notation for the

variable is specified and the basic parameter

assumptions for options B and C are pro-

vided. All percentages are reported in deci-mal format (i.e. 22% is denoted as 0.22).

BS, blood slide; Rx, treatment; AL, artem-

ether–lumefantrine; AB ¼ antibiotic.





that these adults would also be prescribed antibiotics at

the higher rate l1 ¼ 0.87, when compared with l2 ¼0.64. Thirdly, adults who would fall into branch 3 for

option A are moved to branch 4 for options B and C.

Because of this shift, we assume that these adults would

also be prescribed antibiotics at the rate l4 ¼ 0.50 when

compared with l3 ¼ 0.47.

For ‘costs’, our accounting stance is that of a typical

government health facility, and we assume initially that the

health facility bears the full financial costs of microscopy,

AL and antibiotics. Although patients may pay some

portion of diagnostic and treatment costs, and donor funds

are used by the Kenyan Government to purchase drugs,

issues related to ‘who’ pays which portion of the costs is a

distributional issue that does not change the conclusions of

this article on the total amount of such costs. For notation,

cs, ca and cb represent per adult cost of a blood slide, AL

and antibiotics, respectively. As reported in Table 1,

our initial cost estimates are cs ¼ $0.40, ca ¼ $2.4 and

cb ¼ 0.27. While Table 1 documents how these cost

estimates were obtained, we note here that the basic

conclusions of this analysis are not sensitive to these values.

Modelling expected costs

Using the basic four-branch framework for describing

clinical practice from Figure 1, expected costs are

EðCÞ ¼X4

i¼1

piCi ð1Þ

where costs C in eqn (1) include the cost of blood slides, AL

and antibiotics, i ¼ 1, 2, 3 and 4 are the four branches in

Table 1 Initial parameter assumptions not

included in Figures 1 and 2Description

Modelnotation

Initialvalue

Cost of blood slide per adult outpatient cs 0.40 USD*Cost of artemether–lumefantrine per adult outpatient ca 2.4 USD�Cost of antibiotics per adult outpatient cb 0.27 USD�Expert slide positivity rate for non-febrile adult outpatients§ sprEnf 0

Routine slide positivity rate for non-febrile adult outpatients– sprRnf 0.303

Expert slide positivity rate for febrile adult outpatients§ sprEf 0.122

Assumptions for option A and option BSensitivity** SEN 0.667

Specificity** SPEC 0.647

Routine slide positivity rate for febrile adult outpatients�� sprRf 0.391

Positive predictive value�� PPV 0.208Negative predictive value�� NPV 0.933

Assumptions for option C

Sensitivity SEN 0.900Specificity SPEC 0.900

Routine slide positivity rate for febrile adult outpatients�� sprRf 0.198

Positive predictive value�� PPV 0.556

Negative predictive value�� NPV 0.985

* Gross provider cost per malaria slide, which includes costs of microscope, supplies,training, staff time, supervision and overhead for laboratories (Goodman 1999).

� Based on the WHO agreement with the supplier of AL, the instrument that Kenyan MoH

uses to procure the drug.

� Based on the average cost of adult treatment course, which Kenyan MoH pays for themost commonly prescribed antibiotics in study districts.

§ Based on the 0% and 12.2% expert slide positivity rate among non-febrile and febrile

adult outpatients, respectively, who had routine blood slide performed during our earlier

study.– Based on the 30.3% routine slide positivity rate among non-febrile adult outpatients who

had routine blood slides performed during our earlier study.

** The sensitivity and specificity of routine microscopy was 66.7%, and 64.7%, respect-ively, among adult outpatients who had routine blood slide performed during our earlier

study.

�� Computed from eqns (8) to (10) in the text based on sprEf ¼ 0.122 and associated SEN

and SPEC.




Figure 1 and pi the probabilities for each branch, with

p1 ¼ (1 ) p)(1 ) g), p2 ¼ (1 ) p)g, p3 ¼ p(1 ) h) and

p4 ¼ ph. Costs Ci for each branch are computed as

Ci ¼ nðkica þ licbÞ for i ¼ 1; 3 ð2Þ

and

Ci ¼ nðcs þ kica þ lic

bÞ for i ¼ 2; 4 ð3Þ

with

ki ¼ 1� sprRi� �

bi þ sprRi ai i ¼ 2; 4 ð4Þ

From (2), costs Ci for branches 1 and 3 are simply the

number of patients prescribed AL and antibiotics (nki andnli, respectively) multiplied by their respective unit costs

(ca and cb). For branches 2 and 4, costs include the addition

of blood slide costs (cs), but the percentage of adults

prescribed AL from (4), ki, is now a function of the routine

slide positivity rate (sprRi ), the percentage of negative slides

that are ignored (bi) and the percentage of positive slides

that are respected (ai).To estimate expected costs for option A, all the

parameter assumptions used to estimated E(C) based on

eqns (1)–(4) are provided in Figure 1 and Table 1. For

options B and C, all the parameter assumptions used to

estimate E(C) are provided in Figure 2 and Table 1.

Modelling diagnosis errors

Errors from overdiagnosis occur because some adults

who are prescribed AL do not have malaria, while

errors from underdiagnosis occur because adults who are

not prescribed AL do have malaria. For any number of

adult outpatients, n, presenting to a health facility, let

E(no) represent the expected number overtreated and

E(nu) represent the expected number undertreated

patients.

The expected number of adults overtreated for malaria is

EðnoÞ ¼X4

i¼1

pinoi ð5Þ

where

noi ¼ nkið1� sprEi Þi ¼ 1; 2; 3 ð6Þ

and

no4 ¼ n 1� sprR4� �

b4NPVþ sprR4 a4ð1� PPVÞ� �

ð7Þ

For non-febrile adults, overtreatment errors noi for

branches 1 and 2 from eqn (6) depend on the number of

adults prescribed AL, nki and the slide positivity rate of

expert microscopy (sprEi Þ. The assumption here is that sprEi

is a best estimate of ‘true’ malaria; so on average 1 � sprEipercentage of adults in branches 1 and 2 do not have

malaria. As reported in Table 1, the expert slide positivity

rate for non-febrile adults (sprEnfÞ is 0%, suggesting that

non-febrile adults do not have malaria. Data do not exist to

estimate separate values for sprE1 and sprE2, so that sprEnf is

used for both branches 1 and 2 (i.e. sprE1 ¼ sprE2 ¼ sprEnfÞto compute eqn (6). For branch 3, eqn (6) uses the expert

slide positivity rate for adults with fever, sprEf to estimate

the number of overtreated adults for branch 3 (i.e.

sprE3 ¼ sprEf Þ.For branch 4, however, as shown in eqn (7), the

number of adults overtreated with AL, no4, depends on

the number of adults treated with routine negative slides

and the number of adults treated with routine positive

slides. From (7), (1 � sprR4 )b4 shows the percentage of

adults with routine negative slides who are prescribed

AL. The negative predictive value (NPV) shows the

percentage of routine negative tests that were also

evaluated as negative by expert microscopists. Thus,

n(1 � sprR4 )b4 NPV shows the number of adults with

routine negative slides who are prescribed AL but do not

have malaria. Similarly, n sprR4 a4ð1 � PPVÞ shows the

number of adults with routine positive slides who are

prescribed AL but do not have malaria. In sum, the term

in brackets [ ] shows the probability of an overtreatment

error for branch 4.

To complete the model and apply it under varying

circumstances, the basic relationships between background

malaria rates, based on sprEf ; and the accuracy of routine

blood slides needs to be incorporated into the model. For

reference, we note here that

sprR4 ¼ sprRf ¼ sprEf SENþ ð1� sprEf Þð1� SPECÞ ð8Þ

PPV ¼ (sprEf =sprRf ÞSEN ð9Þ

NPV ¼ 1� sprEf� �

= 1� sprRf� ��

SPEC ð10Þ

For fixed sensitivities and specificities of microscopy

practices, SPEC and SEN, eqns (8)–(10) show how sprRf ,

NPV and positive predictive value (PPV) are all logically

linked to the background malaria rate in febrile adult

outpatients (sprEf ). Table 1 provides initial parameter

values for sprEf , SEN and SPEC based on the data for adults

from Zurovac et al. (2006) and the resulting sprRf , NPV

and PPV from eqns (8)–(10). Table 1 also provides the

revised values for sprRf , NPV and PPV for option C, with

90% sensitivity and specificity.

Following similar logic, the expected number of adults

undertreated for malaria is estimated as




EðnuÞ ¼X4

i¼1

pinui ð11Þ

where

nui ¼ nð1� kiÞsprEi i ¼ 1; 2; 3 ð12Þ

and

nu4 ¼ n 1� sprR4� �

ð1� b4Þð1�NPVÞ þ sprR4 ð1� a4ÞPPV� �

ð13Þ

The model for expected costs and expected errors from

overtreatment and undertreatment of adults, as outlined in

eqns (1)–(13), can be estimated for any parameter values

and assumptions, such as the number of output patients

(n), the percentage of febrile outpatients out of total

outpatients (p), the percentages of non-febrile and febrile

outpatients receiving blood slides (g and h, respectively),

background ‘true’ malaria in febrile and non-febrile adults

(sprEf and sprEnfÞ, the accuracy of routine microscopy (SEN

and SPEC), clinical decisions on respecting test results,

joint treatment with antibiotics and the unit costs of blood

slides, AL and antibiotics prescribed.

Ethical approval

The KEMRI national ethical review committee provided

ethical clearance for the study that generated basic data for

this research (reference no. 681).

Results

Expected costs and diagnosis errors per 1000 adult

outpatients

Because expected costs from eqn (1) and expected diag-

nosis errors from eqns (5) and (11) are linear in the total

number of adult outpatients (n), we estimate expected costs

and expected diagnosis errors for options A, B and C for

1000 adult outpatients arriving at a government health

facility with microscopy. These results can then be multi-

plied by any other number to develop estimates for

multiples of 1000 adults.

As reported in Table 2, the expected cost of option A

based on eqns (1)–(4) and initial parameter assumptions

provided in Figure 1 and Table 1 is estimated to be $2154

per 1000 adult outpatients presenting at a health facility.

The majority of such costs are from AL. For option B,

which again is based on eqns (1)–(4) but with assumptions

provided in Figure 2, expected costs fall to $1254 per 1000

adults. For option C, expected costs fall further to $892 per

1000 adults.

Table 2 also reports expected diagnosis errors for the

three options. For option A, 638 adults are overtreated

with AL, while 17 adults are undertreated. For option B,

the expected number of adults overtreated falls to 264,

while the number undertreated increases to 32. For

option C, given the substantial improvement in the

sensitivity and specificity of microscopy, overtreatment

errors fall to 90 adults and undertreatment errors fall to

10 adults.

For the initial assumptions used here, which are based

on recent information on actual practice in government

health facilities in Kenya and reasonable cost estimates for

per adult treatments, we conclude that option B is clearly

preferred to option A for malaria case management in

Kenya in the coming era of AL as a first-line therapy. The

expected cost of option B is 42% lower than option A,

while the costs of AL in particular fall by 54%.

Overtreatment errors fall by 375 adults per 1000 outpa-

tients, although undertreatment errors increase by 14

adults per 1000. While undertreatment errors increase

somewhat, as long as the risks from undertreatment are

no more than 26.7 times as large as the risks from

overtreatment, the total risks from option B are less than

that for option A.

Table 2 Differences in expected costs and diagnosis errors between policy options: results per 1000 adult outpatients

Option A Option B Option C

% cost difference,

option A to B

% cost difference,

option A to C

Expected costs – total $2154 $1254 $892 )42% )59%Expected cost of blood slides $287 $312 $312 9% 9%

Expected costs of AL $1719 $785 $422 )54% )75%Expected costs of antibiotics $148 $156 $156 6% 6%Diagnosis errors Change in errors,

option A to B

Change in errors,

option A to C

Expected number overtreated 638 264 90 )375* )548*Expected number undertreated 17 32 10 14* )8*

* Numbers do not add exactly because of rounding errors.




Option C is obviously better than both options A and B.

Expected costs are 59% less for option C compared with

option A, and the costs of AL are 75% less than that for

option A. Diagnosis errors fall substantially, with errors

from overtreatment falling to just 90 per 1000 adult

outpatients and errors from undertreatment falling to 10

per 1000 adult outpatients. Of the expected total cost

savings from option C, Table 2 shows that 72% of such

savings is from the changes in clinical practice, while the

remaining 28% is from the improvements in the accuracy

of microscopy. Diagnosis errors are less for option C, with

a reduction in underdiagnosis errors of 22 adults per 1000

when moving from option B to option C, suggesting that

improvements in diagnostic accuracy are obviously useful.

Sensitivity analysis

The model developed here in eqns (1)–(14) is applicable to

any situation defined by costs, clinical practices and

accuracy of microscopy. While the initial analysis was

based on actual data on clinical practices and microscopy

accuracy found in the two districts in Kenya studied in

Zurovac et al. (2006) and reasonable estimates of costs and

the joint prescribing of antibiotics summarized in Figures 1

and 2, the model can be organized into a simple spread-

sheet to consider if our basic analysis is sensitive to any of

the assumptions.

Table 3 shows that the conclusions of our analysis from

Table 2 are robust to assumptions related to costs of blood

slides, AL or antibiotics. As shown in Table 3, increasing

substantially the cost of blood slides or antibiotics raises

costs for all options, but option A remains significantly

higher. Clearly, if AL becomes very inexpensive, say $0.50

per adult treated as shown in Table 3, costs of all options

fall dramatically although options B and C still reduce

substantially the number of adults overtreated. Similarly, if

the cost of blood slides or other diagnostic tools increases

substantially, the costs of all options increase but option B

remains preferred to option A. The same conclusion holds

if AL costs fall and blood slide costs increase simulta-

neously.

Table 3 also shows the impacts on costs and diagnosis

errors if this analysis is applied to areas with either lower

or higher background prevalence of uncomplicated malaria

in adult outpatients. In areas with lower prevalence, the

costs of treatment fall somewhat for all options and fewer

undertreatment errors occur. In areas of higher prevalence,

such as 25%, as evaluated in Part B of Table 3, options B

and C remain substantially less costly than option A, with

significantly fewer errors from overdiagnosis. The number

of missed diagnoses in adults increases, as background

prevalence increases to 25%, with an additional 30 adults

are underdiagnosed for option B when compared with

option A. The additional risks to these 30 adults per

Table 3 Sensitivity of results to basic

assumptions: results per 1000 adultoutpatients

Part A: Sensitivity of results to cost assumptions

Costs

Initial

assumptions

Cost of ablood slide

increases from

$0.4 to $1.00

Cost of AL

falls from

$2.40 to $0.5

Cost of antibiotics

increases from

$0.27 to $1.00

Option A $2154 $2584 $793 $2554

Option B $1254 $1722 $632 $1678

Option C $892 $1360 $557 $1315

Part B: Implications of background malaria prevalence

Prevalence ¼ 6% Prevalence ¼ 12.2% Prevalence ¼ 25%

Costs

Option A $2150 $2154 $2161Option B $1218 $1254 $1329

Option C $799 $892 $1083

Diagnosis errors

Expected number overtreatedOption A 676 638 559

Option B 281 264 229

Option C 95 90 81Expected number missed

Option A 8 17 35

Option B 16 32 65

Option C 5 10 20




1000 outpatients are likely to be small in malaria endemic

areas.

Discussion

Given the imperfect microscopy conditions at Kenyan

health facilities, our analysis shows that implementing the

two basic changes in clinical practice as outlined for option

B – only perform blood slides for febrile adults and respect

the results of the tests – would substantially reduce

expected treatment costs, AL drug costs and errors from

overdiagnosis of adult outpatients presenting to a health

facility with functional microscopy when compared with

current practice. While undertreatment errors would

increase by an estimated 14 per 1000 adult outpatients,

because the risks of malaria disease are low in adults, the

benefits of option B based on substantial treatment cost

savings and reduction in overtreatment errors far outweigh

risks associated with a minor absolute increase in under-

treatment errors. Substantial improvements in the accuracy

of microscopy when combined with changes in clinical

practice (option C) would further reduce expected treat-

ment costs and diagnosis errors when compared with

current practice. However, a substantial improvement in

the sensitivity and specificity of routine microscopy, in the

absence of revised clinical practice, does little to reduce

treatment costs or overtreatment errors.

Sensitivity analysis show that both options B and C are

robust to a wide range of assumptions on the costs of

drugs, costs of blood slides and malaria prevalence.

Moreover, successful implementation of either option B or

option C can generate substantial aggregate cost savings on

AL drugs used for adult patients within the government

health sector in Kenya. While functional microscopic

services exist at 24% of all government facilities, 40% of

all adult outpatient visits take place in these facilities

(D. Zurovac & J. Ngigi, unpublished data). If we assume

that these 40% of the adult outpatient visits account for

40% of total treatment costs for adults, implementing only

the changes in clinical practice envisioned as option B

would reduce treatment costs for adults by 17% (24% for

option C) and the total cost of AL drugs prescribed for

adults would fall by 22% (30% for option C). These

figures are probably conservative because cost-per-outpa-

tient visit at facilities with microscopy, which are usually

larger health facilities such as health centres and hospitals,

are likely to cost more than visits to rural dispensaries.

The successful implementation of either option B or

option C would also not alter the overall workload of

laboratories. From Figure 1, our data suggest that 72% of

all adults coming for an initial visit already have a blood

slide performed, and the change in practice envisioned for

option B would require that 78% of adults have malaria

microscopy. This 6% increase in the number of blood

slides is unlikely to burden the capacity of laboratories to

perform blood slides.

Consistent with the findings reported in Malawi

(Jonkman et al. 1995), we also doubt that the reduction in

use of antimalarials associated with either option B or

option C would substantially increase the prescription of

symptomatic and other antimicrobial treatments. Any

additional cost of such prescriptions is unlikely to eliminate

the treatment cost savings from improved clinical practices.

The majority of outpatients in our study sites were

prescribed inexpensive antipyretics and antibiotics anyway,

and we included such drug substitution in our analysis, as

summarized in Figures 1 and 2. As a related issue, patients

(or health workers) may perceive that the prescription of

medications is a signal for good quality of care. As most

adult outpatients would still leave a health facility with

antipyretic and antibiotic prescription, this issue is unlikely

to be of major importance. In most cases, the main

difference to current practices would be an omission of

antimalarial treatment from the existing polypharmacy

prescriptions.

The analysis in this article does not focus on the

interventions that would be needed, and the costs associ-

ated with such interventions, to implement option B or C.

Both options B and C require that health workers change

their current clinical practices. The major change required

is that health workers request a blood slide only for febrile

adults and prescribe AL only for patients with positive test

results. A basic pre-requisite for implementing these

changes in clinical practice is that clinical guidelines

explicitly state age-specific indications for the use of

malaria microscopy and provide instructions as to how

blood slide results should be interpreted. The existing

Kenyan national malaria guideline, which is currently

under revision, does not provide these instructions (MoH

1998). The results of our analysis suggests that, even with

the imperfect microscopy conditions found in government

health facilities, the changes in clinical practices incorpor-

ated into option B for adult patients can be safely

incorporated into national guidelines for AL therapy in

Kenya.

Once clear guidelines exist, however, changing practices

so that health workers adhere to such guidelines will

clearly present challenges. Jonkman et al. (1995) is the

only study in Africa that demonstrated a significant

reduction of unnecessary antimalarial prescriptions in

adults after the introduction of microscopy. This study,

however, was undertaken in a specific setting of an

outpatient department of a referral hospital in Malawi,

where health workers were required to prescribe




antimalarial drugs only to parasitaemic patients (Jonkman

et al. 1995). Larger studies to evaluate the costs and

effectiveness of potential interventions to improve adher-

ence to unambiguous guidelines under operational condi-

tions are urgently needed to provide programmatic

evidence on the factors influencing case management

practices using malaria microscopy.

Finally, several challenges can be expected in the process

of improving the accuracy of malaria microscopy. The

target specified in option C to achieve 90% sensitivity and

specificity of routine microscopy is likely to require a series

of laboratory focused interventions such as retraining of

laboratory technicians, strengthening of the supervision

and establishing currently non-existent quality control

systems. As with the clinical practices, studies evaluating

the costs and effectiveness of various programmatic inter-

ventions to improve and maintain high accuracy of routine

malaria microscopy are urgently needed. At the same time,

investments to improve microscopy needs to be evaluated

in the wider context of multiple diseases for which

microscopy is used as well as new technologies such as

rapid tests for diagnosing malaria.

Acknowledgements

This study received financial support from the Roll Back

Malaria Initiative, AFRO (AFRO/WHO/RBM # AF/ICP/

CPC/400/XA/00), The Wellcome Trust, UK and the Kenya

Medical Research Institute. RWS is a Senior Wellcome

Trust Fellow (#058992). We thank Dr Mike English and

Mathew Fox for comments on the article and Lydia

Mwangi and Lucy Muhunyo for their assistance in data

handling as well as to all health workers and patients who

participated in the original study. This article is published

with the permission of the director KEMRI.

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Corresponding Author Dejan Zurovac, Malaria Public Health & Epidemiology Group, Centre for Geographic Medicine, Kenya

Medical Research Institute/Wellcome Trust Research Laboratories, P.O. Box 43640, 00100 GPO, Nairobi, Kenya. Tel.:

+254 20 2720163; Fax: +254 20 2711673; E-mail: [email protected]




Implications financieres et cliniques du diagnostic microscopique de la malaria chez l’adulte au Kenya

donnees de base Une etude d’observation menee sur la microscopie dans 17 services de sante au Kenya a revele que les benefices potentiels de la

microscopie de la malaria n’etaient pas realises a cause de pratiques cliniques irrationnelles et de la faible precision de la microscopie de routine. Sur base

de ces donnees, nous avons modelise les implications financieres et cliniques de la correction de la pratique clinique et de l’amelioration de la precision de

la microscopie de la malaria chez les patients ambulants adultes sous les directives de traitement utilisant artemether-lumefantrine pour la malaria non

compliquee au Kenya.

methodes Les couts de artemether-lumefantrine, des antibiotiques, de la microscopie de la malaria et du nombre attendu d’erreurs de diagnostic ont

ete estimes par 1000 patients ambulants adultes se presentant dans un service pratiquant la microscopie sous trois scenarios: 1) Option A: pratique

clinique en cours et precision de la microscopie, 2) Option B: pratique clinique corrigee avec la precision microscopique en cours et 3) Option C:

pratique clinique corrigee avec amelioration de la precision de la microscopie. La correction de la pratique clinique a consiste a prescrire la pratique d’un

frottis sanguin pour tout cas febrile adulte et la prescription d’un traitement antimalarique seulement pour les resultats positifs. L’amelioration de la

precision de la microscopie de routine a ete definie pour 90% de specificite et de sensibilite. Dans l’analyse de sensibilite, les implications dans les

changements du cout des medicaments et de la microscopie de la malaria et les changements sous-jacents dans la prevalence de la malaria, ont ete

examinees pour chacune des options.

resultats Le cout de l’artemether-lumefantrine, des antibiotiques et de la microscopie de la malaria ont baisse de 2154$ pour l’option A a 1254 $ pour

l’option B et a 892 $ pour l’option C. 72% des couts evites dans l’option C s’appliquaient aux changements de la pratique clinique et 28% a

l’amelioration de la precision de la microscopie. Sous l’option A, 638 erreurs (faux positifs) de diagnostic par 1000 adultes ont ete effectuees. 375 erreurs

de diagnostic en moins ont ete estimees sous l’option B et 548 en moins sous l’option C. Le nombre de malaria non diagnostiquees restait en general

faible quelque soit l’option. L’analyse de sensibilite a revele que les options B et C etaient toutes les deux robustes pour une large variete d’assomptions

sur le cout des medicaments, des frottis de sang et de la prevalence de la malaria.

conclusion Meme avec des conditions imparfaites de microscopie dans les services de sante au Kenya, l’implementation de pratique clinique corrigee

(option B) reduirait substantiellement les couts et les erreurs de diagnostic en surplus de la malaria. Des interventions supplementaires dans l’ameli-

oration de la precision de la microscopie (option C) peuvent permettre des benefices supplementaires, quoiqu’il soit improbable que l’amelioration de la

microscopie en l’absence de pratique clinique corrigee permette de reduire les couts. Des directives expliquant clairement les indications specifiques a

l’age pour l’utilisation et l’interpretation de la microscopie de la malaria devraient etre urgemment corrigees.

mots cles malaria, microscopie, cout, erreurs de diagnostic, pratique clinique

Las implicaciones financieras y clınicas del diagnostico microscopico de malaria en adultos en Kenia

antecedentes Durante un estudio observacional realizado recientemente en 17 centros sanitarios con microscopıa en Kenia, se demostro que los

beneficios potenciales de la microscopia de malaria no se estaban dando debido a una practica clınica irracional y a una baja precision en la microscopıa

de rutina. Utilizando estos datos, modelamos las implicaciones clınicas y financieras de unas practicas clınicas revisadas y un aumento en la precision de

la microscopia para malaria, entre adultos que acudıan a consultas externas por polıtica de tratamiento con artemeter-lumefantrina para malaria no

complicada en Kenia.

metodos Se estimaron el coste de artemeter-lumefantrina, de los antibioticos y la microscopia para malaria ası como el numero esperado de errores en

el diagnostico de malaria por cada 1,000 pacientes adultos que se presentaban en un servicio sanitario con microscopio bajo tres escenarios:1) practica

clınica y precision de la microscopıa actuales (Opcion A); 2) practica clınica revisada y precision de la microscopıa actual (Opcion B); y 3) practica

clınica revisada con mejora en la precision de la microscopıa (Opcion C). Se definio la practica clınica revisada como el hacer una gota gruesa a todos los

adultos febriles y prescribirles tratamiento antimalarico solo a los que obtuviesen un resultado positivo. Una mejora en la precision de la microscopıa de

rutina se definio como una sensibilidad y especificidad del 90%. En el analisis de sensibilidad se examinaron para cada opcion las implicaciones de

cambio en el coste de los medicamentos y la microscopıa de malaria ası como los cambios en la prevalencia de la malaria de fondo.

resultados El coste de artemeter-lumefantrina, antibioticos y la microscopia de malaria disminuyo de $2,154 bajo la Opcion A a $1,254 bajo la

Opcion By $892 bajo la Opcion C. De los ahorros en costes de la Opcion C, un 72% correspondıa a cambios en las practicas clınicas y 28% era de

mejoras la precision de la microscopıa. Bajo la Opcion A se sobrediagnosticaron como malaria 638 de cada 1,000 adultos; en la Opcion B y C se

estimaron 375 y 548 menos errores de sobrediagnostico respectivamente. El numero de diagnosticos de malaria omitidos fue en general bajo en todas las

opciones. El analisis de sensibilidad mostro que ambas opciones By C eran robustas a un amplio rango de supuestos sobre el coste de los farmacos, el

coste de las gotas gruesas y la prevalencia de malaria.

conclusiones Aun con las condiciones imperfectas de microscopıa existentes en las instalaciones de Kenia, la implementacion de una practica clınica

revisada (Opcion B) reducirıa sustancialmente los costos y errores debido al sobrediagnostico de la malaria. Intervenciones adicionales para mejorar la

precision de la microscopıa (Opcion C) podrıan alcanzar mayores beneficios; aunque la mejora de la microscopıa en ausencia de una practica clınica

revisada es poco probable que genere ahorros significativos en los costos. Es urgente revisar las directrices para que expongan explıcitamente las

indicaciones, especificadas por edad, del uso y la interpretacion de la microscopıa para malaria.

palabras clave malaria, microscopıa, costo, error de diagnostico, practica clınica




The financial and clinical implications of adult malaria diagnosis using microscopy in Kenya

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