Cost-effectiveness of a successful schistosomiasis control programme in Cambodia (1995–2006)

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Contents lists available at ScienceDirect

Acta Tropica

journa l homepage: www.e lsev ier .com/ locate /ac ta t ropica

ost-effectiveness of a successful schistosomiasis control programme inambodia (1995–2006)

avide Crocea, Emanuele Porazzia, Emanuela Fogliaa, Umberto Restelli a, Muth Sinuonb,uong Socheatb, Antonio Montresorc,∗

Centre for Research on Health Economics, Social and Health Care Management (CREMS), Università Carlo Cattaneo - LIUC, Castellanza (VA), ItalyNational Center for Parasitology, Entomology and Malaria Control, Ministry of Health, CambodiaWHO, Neglected Tropical Diseases, 20 Avenue Appia, Geneva, Switzerland

r t i c l e i n f o

rticle history:eceived 31 August 2009eceived in revised form9 November 2009ccepted 28 November 2009vailable online 3 December 2009

eywords:ealth technology assessmentost-effectiveness analysisost-benefit analysis

a b s t r a c t

Following preventive chemotherapy covering the entire population in the two endemic regions in Cam-bodia, the prevalence of schistosomiasis dropped from 77% in 1995 to 0.5% in 2003. The study presentedhere reports on the running cost of the control programme, and evaluates its cost-effectiveness andcost-benefit.

Financial costs were assessed using data taken from the annual reports of the National Center for MalariaControl, the Cambodian institution responsible for the control activities. Other data were collected frominterviews with provincial and district staff. The analysis was conducted from the point of views of theCambodian Ministry of Health and that of the society, and the comparison was undertaken using the“do-nothing” option.

The cost to treat an individual for the 9 years period of the implementation phase was 9.22 USD (1.02

chistosomiasisull costing approach

per year), the cost for each severe infection avoided was 61.50 USD and 6531 USD for each death avoided.The drug cost corresponds on average to 17.34% of the programme’s implementation cost. The cost ofbringing one severely infected individual of productive age to complete productivity, was estimated at114 USD and for 1 USD invested in the programme the return in increased productivity, for the economicsystem, was estimated to be 3.85 USD.

The control programme demonstrated significant economical advantages. However, its costs are toorted b

high to be entirely suppo

. Introduction

Schistosomiasis is one of the most prevalent parasitic infectionsn the world. It is endemic in 76 countries and continues to be aublic health problem in the developing world (Engels et al., 2002;teinmann et al., 2006). In Cambodia, the parasite responsible forhe disease is Schistosoma mekongi.

The parasite is transmitted by contact with contaminated waterWHO, 2002; Gryseels et al., 2006). At an early stage of infec-ion, lesions of the liver can be detected (Hatz, 2001). At a latetage symptoms and signs associated with S. mekongi infectionnclude cachexia, hepatosplenomegaly, stunting and retardation of

uberty, portal hypertension, ascites and rupture of oesophagealarices (Biays et al., 1999). Pathology associated with the infec-ion consists of periportal thickening and portal vein enlargementHatz, 2001). Severely infected individuals experience a significant

∗ Corresponding author.E-mail address: [email protected] (A. Montresor).

001-706X/$ – see front matter © 2009 Elsevier B.V. All rights reserved.oi:10.1016/j.actatropica.2009.11.011

y the Cambodian Ministry of Health.© 2009 Elsevier B.V. All rights reserved.

reduction of working capacity and productivity (King et al., 2005). Inindividuals continuously exposed to infection without treatment,the disease progresses into different degrees of severity (infectionof light, moderate and high intensity) and can lead to death (Warrenet al., 1993).

Large scale preventive chemotherapy is the public health strat-egy recommended by World Health Organization (WHO) for thecontrol of helminthic diseases such as schistosomiasis (WHO,2006). The control strategy consists of the annual administration ofpraziquantel to the population at risk in the endemic areas (WHO,2002).

The treatment, administered at regular intervals, eliminatesmost of the infecting schistosomes and prevent the developmentof severe morbidity. Since no infective stages of the parasite arecontaminating water, reinfection takes place, however most of the

infected individuals present “light intensity” infection because theannual interval between two treatments allows only few schisto-somes to complete the cycle in the host.

Praziquantel has rare side effects which include nausea andabdominal pain. These do not require treatment (Stelma et al.,

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995). The frequency of side effects is related to the intensity ofhe infection in the population and therefore is higher during therst year of the control programme after which it progressivelyecreases over the following years (N’Goran et al., 2003).

The first case of schistosomiasis in Cambodia was diagnosed in968 (Biays et al., 1999). The activities used in the collection ofata about this pathology were interrupted due to the presence ofhe Khmer Rouge regime. From the last months of 1994, with theall of the political regime, the monitoring activities started againnd several severe cases of schistosomiasis were diagnosed in 20illages in Kratie Province (Stich et al., 1999).

In the last weeks of 1994 the Cambodian Ministry of HealthMoH), started regular preventive chemotherapy in the North-Eastrovinces of Cambodia. The responsibility for the control activi-ies was given to the National Center for Malaria Control (CNM),ith the technical support from Medecins sans Frontières (MSF) andHO. As of 1995, the area of intervention increased from the 20

illages where schistosomiasis was originally reported, to includell new areas that were progressively identified; this brought theotal to approximately 110 villages.

The programme was based on a Mass Drug AdministrationMDA) carried out by CNM staff, who reached the villages usingoats and local volunteers. The control programme presented aecreasing number of difficulties each successive year: the massistribution of praziquantel were increasingly accepted by the localommunities.

. Materials and methods

The primary objective of the study was to provide informationbout the effectiveness and the cost of the programme, throughhe evaluation of the incremental cost-effectiveness of the pub-ic health intervention for schistosomiasis control, taking the MoHiewpoint. The comparison was undertaken with the “do-nothing”ption, in which the MoH does not implement any control activity,s before 1995.

To achieve this primary objective, a health technology assess-ent (HTA) approach, based on the Guidelines of the Canadiangency for Drugs and Technologies in Health (2006), was used inrder to evaluate the most important aspects to calculate the costnd the effectiveness of the programme.

HTA is a systematic review of existing evidence that providesn evaluation of the effectiveness, cost-effectiveness and impactoth on patient health and on health care systems (Fox-Rushby

nd Cairns, 2005). We calculated the cost for each averted death,or each severe infection averted and for each infection averted. Therganizational impact, the budget impact, the equity (Goodman,998) and the generalizability (Sculpher et al., 2004) of the pro-ramme implementation were also assessed.

able 1ost categories of the schistosomiasis control programme in Cambodia.

Cost category Cost element

Initial investment Staff salaries, transports, materials, questionnaire distrib

Coordination and overhead Salaries and per diem: CNM officers, MoH provincial officVehicle: purchase, maintenance, insurance, national taxeUtilitiesb: CNM cost for electricity, telephone, water, builprogramme and guards

Distribution cost Activities planning, drugs procurement (delivery at Phnofuel and boats renting), welcome costs (province and villposters)

Survey cost Staff per diem, transport (cars fuel and boats renting), eq

a The salary of staff involved in the procurement and in the administration of the progrb No analytical accounting scheme was available to calculate the utility costs in the

rogramme, assuming that the expenditures in each of the five institutional programmesmplementing each the programme.

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2.1. Epidemiological data

Epidemiological data were collected with periodical parasito-logical surveys: every year, an average of 2000 stool samples fromindividuals in randomly selected villages were analyzed with theKato-Katz method. Annual surveys were also conducted in primaryschools of five sentinel villages (Sinuon et al., 2007).

There was active search and follow-up of cases of severe mor-bidity due to schistosomiasis during the mass treatments and theparasitological surveys and the age and sex of the cases identifiedwere recorded.

The data were analyzed and internal reports and scientificpapers were regularly published (Urbani and Socheat, 1997; Stich etal., 1999; Urbani et al., 2002; Ohmae et al., 2004; Sinuon et al., 2007).A linear model (Davison, 2003) was used to estimate the effective-ness of the programme, based on the prevalence data collected bythe operators (Sinuon et al., 2007).

2.2. Economic data

Most of the economic data were taken from the “Annual ProgressReport of the National Center for Parasitology Entomology andMalaria Control” (CNM, 2006). Additional data were collected fromdocuments published by the National Institute of Statistics of theCambodian Ministry of Planning (National Institutes of Statistic,2009) and by WHO. Further information was taken from interviewsadministered to experts involved in the programme. In the periodunder evaluation, initially Médicins Sans Frontières and then WHOwere providing financial support (that has been included in the costevaluation) and technical assistance through their local offices (themonetary value of this technical support has not been included inthe cost evaluation).

Cost data were recorded in Cambodian Riel and than convertedinto USD with an exchange rate of 0.00025 (average exchange ratein the first 6 months of 2006) and referred to 2006.

Four different categories of cost were taken into consideration,both direct and indirect (Finkler and Ward, 1999): initial invest-ment, coordination and overhead, distribution and survey costs,see Table 1.

The time spent by village health workers (VHW) was valued atthe same level as the government salary (55.20 USD/months, costto the company) and the required number of VHW was 1 per 400inhabitants.

We calculated the incremental cost-effectiveness ratio (ICER)

(Tan-Torres Edejer et al., 2003) comparing the programme imple-mentation scenario, as the new technology, with the “do-nothing”option, as the already existing technology.

The secondary objective of the study was to estimate the cost-benefit of the intervention, from the perspective of the society,

Source

ution and questionnaire analysis Interview, CNM documents

ers, volunteersa

s, amortization (7 years);ding maintenance, administration of the

Annual report of CNM, interview

m Penh), staff per diem, transport (carsages lunches), social marketing (T-shirt,

Interview, International Drug PriceIndicator Guide, annual report ofCNM

uipment kits for Kato-Katz test and scale Interview, annual report of CNM

amme and of the CNM drivers are valued as distribution costs.CNM office (Phnom Penh). The costs were extrapolated for the schistosomiasisof CNM, are proportional to the number of people and number of cars available for

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valuating the increases in productivity that were not taken intoonsideration from the MoH perspective, to investigate the sus-ainability of the programme.

.3. Impact on productivity

The impact of preventive chemotherapy on productivity waseasured taking into account the decrease in the number of severe

ases of schistosomiasis and deaths. The proportion of severelynfected and the number of deaths was considered to decrease lin-arly, throughout the implementation phase, to be 0 in 2003. Theumber of severely infected individuals of productive age (15–59ears), was extrapolated combining the total number of severelynfected individuals and the age structure of the population in Cam-odia. The number of severely infected individuals was consideredo be distributed equally in all age groups, this was a conservativessumption since, from the available data on morbidity indicatehat the majority of the cases of severe schistosomiasis was in theroductive age. The productivity of 1 life year was considered toe 154.11 USD in 2006, equal to the pro-capita Cambodian GDP inhe agriculture and fishing sectors, as these are the main economicctivities in the two provinces. The decrease in productivity waslso evaluate with a conservative approach each individual withevere schistosomiasis was estimated to be 50% (Guyatt and Evans,995) and no reduction in productivity was taken into account for

ndividuals with infection of moderate/high intensity.We assumed a situation of full employment in the area.Additional analyses were performed to evaluate the robustness

f the results, using two different methodologies: sensitivity analy-is, assuming a ±30% change in the per diem salary, a ±50% changen fuel cost and a ±10% change in the cost of utilities (Saltelli etl., 2000), and “Monte Carlo” method, applied to salaries, with 100terations (Doubilet et al., 1985). For both approaches, the tempo-al horizon was fixed at 5 years, the value of annual volatility wasxed at plus or minus 30%. The variation was considered to elapset the end of each year. The cost categories used for the sensitivitynalysis were chosen because they are the ones most exposed toarket variations, time and the most relevant for the total cost of

he health programme.

.4. Phases of the control programme

To facilitate the analysis and the processing of the economicata, the schistosomiasis control programme was divided intohree phases: planning and start up, implementation and main-enance, as suggested in literature (Johns et al., 2003). The costncurred in the planning and start-up phase (including studies andurveys conducted for the identification of the infected areas) weremortized to the 9 years of the implementation phase. The lengthf the implementation phase was 9 years: from 1995 (first drugistribution) up to and including 2003 (when no schistosomiasisases were identified by parasitological surveys). For the mainte-ance phase, expenditure for 3 years (2004–2006) was analyzednd some suggestions on how to contain the cost of this phaseere provided. This phase was conducted after reaching the “noore cases” situation.

. Results

The activities conducted during the 9 years of the imple-entation phase reduced the schistosomiasis prevalence from an

stimated 77% (61,600 individuals infected) in 1995 to an estimated.5% in 2003 (Fig. 1). No cases were found with the parasitologicalurvey carried out from 2003 to 2006. However, due to the lowensitivity of the Kato-Katz method at low intensity of infectionYu et al., 2007) and the interval of confidence of the results of the

Fig. 1. Estimated population at different intensity of infection with S. mekongi in1995, before the initiation of the control activities and in 2006 after 9 years ofintervention.

survey, the presence of 400 cases of low intensity was estimated.The effectiveness of the 9 years programme in reducing the numberof infected individuals was calculated to be 99.35%. This should beconsidered a conservative hypothesis.

Before intervention the total number of severe infections wasestimated to be 12,000 per year requiring approximately 250hospital admissions each year. The residual classes of infection(moderate and light intensity infections) were estimated to be49,600, requiring approximately 1000 consultations each year. Theyearly number of deaths due to schistosomiasis was estimated to be25 per year. Fig. 1 graphically presents the morbidity due to schisto-somiasis in Cambodia before and after the control intervention. Weassumed that, without control intervention, the epidemiologicalsituation would not have changed.

The cost of the “do-nothing” option was estimated to be 20,000USD per year (the evaluation is based on 2006 costs data), tak-ing into account three consequences of the infection: outpatientconsultations (1000 consultations at 2 USD/each), hospital admis-sions (200 admissions at 50 USD/each) and surgical interventions(50 interventions at 160 USD/each), death and reduced productiv-ity were not valuated because, despite representing a significantloss for a family, they do not constitute a cost for the MoH. Thiseconomic information was taken from interviews administered toCNM experts and Provincial Hospital staff. The total costs of the“do-nothing” option, for the 9 years of the implementation phase(1995–2003) are equal to 180,000 USD.

In the intervention option: the total cost of the implementa-tion phase (1995–2003) is evaluated at 657,982 USD, details on thedifferent cost categories are presented in Table 2. The additionalcost of implementation phase due to the treatments still to be pro-vided to infected individuals was estimated at 80,000 USD bringingthe total cost of this option to 737,982 USD. During this phase theestimated annual cost per treated person is 1.02 USD. Using thisapproach, the drug cost corresponds to 17.34% of the programme’simplementation cost.

From 2004 to 2006 the annual cost of the maintenance phasewas on average 76,827 USD. Drug distribution cost (drug procure-ment and administration) represent 73.95% of the total cost.

The yearly cost of the programme is gradually diminishing overthe years from 99,754 USD in 1997, to 72,511 USD in 2006 (all theamount were calculated at 2006 constant price).

The results from the variability analysis show that the changesin salaries (±30%), fuel (±50%) and utilities (±10%) would not have

high impact on the total programme cost (±11.32% increasing anddecreasing all the variables). The “Monte Carlo” Analysis applied tothe most relevant costs in percentage and with the major proba-bility to increase salaries does not show any unexpected variation,reinforcing the robustness of the results.

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Table 2Details of costs of schistosomiasis control programme in Cambodia by cost category.

Start-up and implementation activities (USD) Maintenance (USD)

1995 1996 1997 1999 2000 2001 2002 2003 Total 2004 2005 2006

Initial investment 786 786 1,571 1,571 1,571 1,571 1,571 1,571 11,000 – – –Coordination and overhead 10,747 10,747 20,760 19,295 18,563 17,830 17,097 16,365 131,403 15,632 13,068 12,335

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Distribution cost 34,653 34,653 67,918 65,142 63,Survey cost 4,752 4,752 9,504 9,504 9,

Total 50,937 50,937 99,754 95,512 93,

The cost of treating an individual for the 9 years of the interven-ion phase was 9.22 USD. The yearly cost per infection avoided is.33 USD. The cost per each case of severe infection avoided is 61.50SD and the cost per each death avoided is 6531 USD. During theyears of the implementation phase, the total number of avoidedeaths was estimated to be 113, decreasing linearly from 25 in therst year to be 0 in 2003.

The cost-effectiveness value (ratio between the cost and theffectiveness of the programme implementation) per treated per-on for the 9 years implementation phase of the control programmes equal to 9.29 USD per person.

The ICER (representing the cost to increase the effectiveness ofne unit) resulted to be 7.02 USD per capita.

The incremental cost-effectiveness plan (Fig. 2) compares thedo-nothing” option with the implementation phase results andhows the complete rationality of the choice to treat the wholeopulation through an MDA. The cost increase is accompanied by areater increase in effectiveness. This result suggests a dominanceor the choice to implement the programme with respect to thedo-nothing” option.

From the point of view of society, it is important to underlinehat the schistosomiasis control programme increased the societalroductivity, giving to 6479 severely infected individuals between5 and 59 years of age the possibility to return to full productivity.he cost of bringing one severely infected individual of produc-ive age to complete productivity was estimated to be 113.91 USD

737,982 USD/6479 severely infected individuals).

809 individuals, of the 6479 severely infected in 1995, are esti-ated to recover to complete productivity every year in whichass drug administration is conducted. This, considering the

ig. 2. Incremental cost-effectiveness plan, comparing the “do-nothing” option andntervention programme, based on costs per protected individual.

62,356 60,997 59,589 449,051 58,201 56,812 55,4249,504 9,504 9,504 66,528 9,504 4,752 4,752

91,271 89,150 87,029 657,982 83,337 74,632 72,551

productivity of severely infected individuals before the implemen-tation of the control programme to be 50% (Guyatt and Evans, 1995),correspond to a productivity gain of 14,562 year, to which the pro-ductivity gained from the averted deaths (3546 years) should beadded for a total of 18,108 full year of productivity gained. The totalfinancial gain in productivity is estimated to be equal to 2,790,623USD (18,108 years × 154.11 USD).

The necessary investment within the programme to increasesocietal productivity by 1 USD, is 0.26 USD (737,982 USD/2,790,623USD). For 1 USD invested in the programme, the return in increasedproductivity is 3.84 USD.

Taking the MoH viewpoint, the cost-benefit value (CBV) is 0.24.The benefits were estimated to be 180,000 USD (saved costs), whilethe cost of the programme was 737,982 USD.

The yearly cost per capita of the maintenance phase (0.96 USD)is representing 15.74% of the total government per capita expendi-tures on health (WHO, 2007).

If we exclude the drug cost, on the hypothesis that this cost willbe covered by an external agency, the per capita expenditure is0.76 USD, representing 12.46% of the total government per capitaexpenditure on health.

In terms of organizational impact analysis of the control pro-gramme, the number of people involved was estimated as 14 healthstaff, with an average commitment of 3 months each year and 10public servants with an average commitment of 1 month each year,this corresponds to less than 1% of the staff of the MoH that includesover 10,000 midwives and nurses (WHO, 2000).

No ethical or equity problems have emerged from the study.Rather, the more marginalized and poor population groups benefitto a larger extent from the intervention since drugs are admin-istered free of charge, for those who present themselves at thedistribution point, in each endemic village. This also allows accessto treatment for the more disadvantaged groups of the population.

4. Discussion

This is the first study that applies an HTA approach to a suc-cessful schistosomiasis control programme that lasts over 12 years.In all the available economic evaluations, the sole direct costs ofcontrol programmes were taken into consideration, or a shorterprogramme implementation was considered (Kirigia et al., 2000;Zhou et al., 2005; Brooker et al., 2008).

The progressive reduction of the costs of the programme, wasdue to an increase in the efficiency of the personnel involved, to areduction of the number of surveys, to an increase in participationof the target population, in addition to a reduction of the numberof side effects from praziquantel requiring follow-up.

The cost per death avoided calculated for this intervention(6531 USD in 9 years) is in the order of magnitude of the onesobtained by insecticide-impregnated bed nets used for malaria con-

trol (Kikumbih et al., 2005) and vaccination campaign for measles(Uzicanin et al., 2004) that are considered extremely cost-effectiveinterventions. However, mortality is a relatively rare outcome ofschistosomiasis and the most important effects are on morbiditythat was eliminated by preventive chemotherapy at very low cost.

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In the review of the relevant literature performed, the yearlyosts per infection avoided are within a range of 3.10 USD (Gryseels,989) and 12.43 USD (Guyatt and Evans, 1995), but these studiesonsider only the direct costs of the programmes.

The study demonstrated a lower cost of the “do-nothing” optionrom a MoH perspective; however, the low cost of this option is

consequence of the unclear symptomatology of schistosomia-is, that results in a very limited number of individuals presentinghemselves to health units in order to receive treatment. This islso the reason why WHO recommends periodical chemotherapys public health intervention for the control of schistosomiasis: inbsence of mass drugs administration the majority of the schisto-omiasis cases are untreated, and the morbidity due to the diseaseould reach high levels.

Taking into consideration the perspective of the society andncluding the increase in productivity, the programme has anxtremely favourable cost-effectiveness: over 2.7 million USD ofncrease in productivity at a cost of less than 750,000 USD with

return of investment that is greater than the one obtained byaccination programmes (Andre et al., 2008).

We consider that several additional economic advantages areccrued with the control of schistosomiasis: for example, we did notake into consideration the additional benefits due to the elimina-ion of infections of moderate/high intensity, the increase in schoolttendance and performances that are well recognized followingchistosomiasis control (Nokes et al., 1999; Jukes et al., 2002). Theseast effects were difficult to be quantified in Cambodia, because

as not able to exactly quantify of the poor maintenance of schoolecords.

Despite the very good cost-effectiveness obtained and the rela-ively low annual cost of the programme, the cost of the programmeer beneficiary (1.02 USD) represents a relevant part of the perapita expenditure on health of the Cambodian government (6.1SD). The same situation can also be observed in the case whererugs are provided by an external donors. This cost is consideredo be too high, to be sustained by the MoH, especially in the main-enance phase, when the number of schistosomiasis cases is veryow.

Using the HTA approach, it is clear how the programme imple-entation scenario should be preferred to the “do-nothing” option.Considering the organizational impact, the staff and the pub-

ic servants needed to implement the programme are less than 1%f the total MoH staff, which includes over 10,000 midwives andurses (WHO, 2000). Therefore, the work load of the MoH person-el will not vary considerably due to the schistosomiasis controlrogramme implementation and the MoH could easily identify thetaff who will participate in the programme.

In terms of generalizability, the programme is simple and easy toe managed and implemented; it is performed during few monthsvery year. The drugs used are available on the international marketnd their cost has constantly decreased in the last decade (in 2006t corresponds to 22% of the total cost of the programme). Theseactors demonstrated a good generalizability of the programme forther countries.

The small dimension of the endemic areas, the low populationensity and the difficulties in transport make the generalization ofhe economic results in Cambodia appropriate for countries withimilar situation, like Laos PDR, however, generalization more dif-cult for African countries in which normally the schistosomiasisndemic areas cover large part of the surface of the country.

The high impact of the control programme on the MoH expen-

iture could be an indication of the need for the donor communityo support endemic countries in NTD control.

Without external support there is a risk that the local decisionakers could interrupt the control programme to invest in otherore prevalent diseases. The experience from Lao People’s Demo-

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cratic Republic (Khamkeo and Pholsena, 2009) demonstrated thatif the intervention is interrupted, within 10 years the benefits ofthe control programme could be completely lost and therefore theepidemiological situation of schistosomiasis could return to thepre-intervention level. Hence the necessity to find a way to reducethe cost (for example, organizing drugs distribution every 2 years)and not to interrupt the intervention.

Future scenarios should consider the hypothesis to continue themaintenance phase, in order to reduce the cost related to schisto-somiasis within the country. The possibility to measure the socialimpact of the implementation phase of similar programmes willprobably show additional advantages and a higher cost saving incomparison to the one estimated for this study.

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