Cost-effectivenessMODS showed an average cost-effectiveness rate (ACER) of 120,86 and GeneXpert of 103,79.GeneXpert showed an incremental cost-effectiveness rate (ICER) of 103,79 and MODS of 203,12.

Sensitivity analysis – One way

Average cost-effectiveness rate Average cost-effectiveness rate

Figure 1. One way sensitivity analysis through all the possible values for key values.

CFR: Case fatality rate; TB: Tuberculosis.

Probabilistic sensitivity analysis

Difference in Effects (LYG) Willingness to pay (2013 USD)

ICER MODS ICER Xpert ICER MODS ICER Xpert

Figure 2. Cost-effectiveness plane. Figure 3. Cost-effectiveness probability

LYG: Life-years gained. curve. CEP: cost effectiveness probability.

Variable Value Standard Error Distribution

MODS costs 2,119,245,63 USD 120,000 USD Gamma

Xpert costs 1,767,638.43 USD 100,000 USD Gamma

Smear 896,310.82 USD 50,000 USD Gamma

% HIV 6% 2% Gamma

SensitivityMODSXpert

96%88%

2%5%

Beta

HIV SensitivityMODSXpert

88%80%

2%4%

BetaBeta

Prob not Dx smear 52% 10% Beta

Prob not Dx smear HIV 65.5% 10% Beta

Prob Dx smear 48% 10% Beta

Prob Dx smear HIV 34.5% 10% Beta

TB incidence 220/100000 100/100000 Beta

TB mortality 53/100000 45/100000 Beta

TB incidence in HIV 330/100000 100/100000 Beta

TB mortality in HIV 177/100000 10/100000 Beta

CFR Dx 0.08 0.03 Beta

CFR not Dx 0.4 0.13 Beta

CFR HIV Dx 0.11 0.01 Beta

CFR HIV not Dx 0.62 0.09 Beta

Table 2. Variables introduced in the calculations. CFR: Case fatality rate; SE: standard error.

ConclusionsBoth techniques were considered cost-effective considering a willingness to pay threshold equal to the GDP of Mozmbique.

Due to uncertainty in the data we were not able to conclude that GeneXpert was more cost-effective than MODS but, a tendency is observed towards Xpert MTB/RIF being more cost-effective.

MODS sensitivity HIV

MODS sensitivity

HIV prevalence

TB incidence

TB in HIV incidence

TB mortality

CFR on treatment

CFR not on treatment

CFR HIV on treatment

CFR HIV not on treatment

Xpert sensitivity HIV

Xpert sensitivity

HIV prevalence

TB incidence

TB in HIV incidence

TB mortality

CFR on treatment

CFR not on treatment

CFR HIV on treatment

CFR HIV not on treatment

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0 5000 10000 15000 20000

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IntroductionTuberculosis (TB) is a global public health priority. In 2012 there were an estimated 8.6 million new cases of TB (range 8.3-9.0) globally and 1.3 million deaths due to TB.1

Diagnosis of TB is challenging and although reliable meth-ods exist on the market, they are in general slow and expen-sive or they are not very reliable. Globally, only 66% of the estimated TB cases are diagnosed, mainly due to poor diag-nostic means in low income countries (LIC).

TB diagnostic tests have had a tremendous development and new rapid methods, based on PCR, for TB diagnosis are on the market. GeneXpert MTB/RIF® has been endorsed by WHO and recommended for expansion at district level in LIC. Nev-ertheless the cost of this equipment is relatively high without long-term external funding.2

Microscopic Observation Drug Susceptibility (MODS) assay is a cheap and low-complexity liquid-culture based technique for the diagnosis of TB infection and TB drug resistance.3,4 It has been evaluated in African settings and WHO has endorsed the assay for DST. Published numbers for the cost/test for the MODS assay have varied, ranging from as cheap as 0.72 USD for the diagnosis of TB only to 7.31 USD in the most expensive and complete calculation.2,5

Mozambique is considered by the WHO as a high TB / high HIV burden country. It has a TB incidence of 553(CI

95% 380-747)/

100‘000 population; that is 130‘000 new cases every year and 63% of them are among HIV-infected patients. The nationwide HIV prevalence is 12%.6

We aimed to compare GeneXpert MTB/rif Versus MODS in terms of potential cost-effectiveness in a rural Mozambican district.

MethodsSettingAncuabe district is a rural area in the north of the country located in Cabo Delgado, one of the poorest provinces in Mo-zambique. Ancuabe has an extension of 4606 km2, and a popu-lation of 118‘926 inhabitants. The estimated HIV prevalence is about 6% (18). All TB diagnoses are based on clinical diagnosis and sputum smear microscopy. There are no microbiological culture facilities. The majority of the burden of care delivery in Ancuabe is provided by non-physician clinicians.

Costing studyThe health provider perspective was chosen. A bottom-up cost-ing method was used. Costs were identified through a thor-ough evaluation of types of resources needed, unit costs and total amount. Values for the unit costs were identified with up-to-date pro-forma invoices from different suppliers, official prices of the official Mozambican service providers and the official salary scale of the Mozambican Health Service. Capital costs were annualized with useful life estimates obtained from World Health Organization tables (www.who.int/choice/costs/prices_t4/en/index.html). As estimates for Mozambique were not available estimates for Kenya were used. When estimates for different equipment were not available in the WHO tables a 5 year useful life was assumed except for the GeneXpert Module where a 4 year useful life was assumed in accordance with previous publications.7 A 3% annual discount rate was applied for future costs.

Effectiveness estimationThe latest Life tables for Mozambique (2011), from the WHO Glob-al Health Observatory (http://apps.who.int/gho/data/view. main-wpro.61120?lang=en) were used to assess the impact of the installation of the different techniques. Reduction of the yearly probability of death due to the introduction of the tech-niques was calculated as:

P(D|t) = P(D| - t) - TB mortality + TB mortality * RRTP(D|t) = Probability of death with the technique installed. P(D|-t) = Probability of death without the technique installed.TB mortality = Global TB Mortality in Mozambique. RRT = relative risk of death with the technique versus the base case (smear micros-copy).

RRT was calculated as:RRT = MWT / TBmortality

MWT = Mortality with the technique installed.Mortality with the technique was calculated as:MWT = TBincidence * P(Dx|tb) + TBincidence * P(- Dx|tb) * P(D|- d)P(Dx|tb)=Probability of being diagnosed with TB when you have it.P(D|d)=Probability of death on treatment drugs.P(-Dx|tb)=Probability of not being diagnosed when you have tb.P(D|-d)=Probability of death not on treatment.

Official 2013 WHO estimates for Mortality and TB Incidence where used to fit the Probability of death not on treatment.2 This way of calculation is analogous to the model WHO devel-oped in 2012 for the calculation of TB deaths estimates.2

Estimated mortality introducing the techniques was calcu-lated varying the probabilities of diagnosis and not diagnosis according to the sensitivities and specificities of the techniques.

Input parameters where obtained from local registries, pub-lished data of sensitivity and specificity for the different tech-niques, official WHO estimates for TB incidence, mortality and case detection rate and from the life tables for Mozambique of the WHO Global Health Observatory.

As the mortality and the effectiveness of the techniques is not equal in children as in adults, we did not include children in the study.

Cost-effectivenessThis allowed us to calculate the average cost-effectiveness ra-tio for each technique and the Incremental cost-effectiveness rate for MODS and GeneXpert compared to smear microscopy. The techniques were considered cost-effective below a will-ingness-to-pay threshold equal to the 2012 per capita Gross Domestic Product (GDP) of Mozambique (565.16USD).8

Sensitivity analysisA one way sensitivity analysis as well as a probabilistic sen-sitivity analysis was undertaken.

ResultsCosts

MODS GeneXpert Smear

Capital costs 217‘587,70 216‘664,77 6‘918,44

Maternal and equipment 49‘770,85 3110,67 7776,69

Laboratory rehabilitation 1555,33 1555, 33 1555, 33

Equipment transport 5949,20 13‘457,96 4043,88

Training 60‘673,79 17‘627,18 0

Human resources 909‘873,50 545‘924,10 545‘924,10

Reagents 201‘717,56 402‘058,32 41‘458,20

Maintenance 47‘431,94 13‘998,05 3‘110,68

Treatment costs 397‘698,13 363‘852,20 194‘055,97

Overheads 227‘070,96 189‘389,83 96‘581,20

Total costs 2‘119‘328,98 1‘767‘638,43 901‘424,50

Table 1. Cost estimates for the implementation during 90 years of the three different tech-niques in the Ancuabe district. Units are in 2013 USD. Costs have been annualized and a 3% yearly discount rate has been applied.

Difference in effectsMODS was estimated to have the potential to save 10‘076.49 life-years. GeneXpert was estimated to have the potential to save 8‘345.10 life-years.

0 200 400 600 800 1000 0 200 400 600 800 1000

Evaluation of cost-effectiveness of MODS Vs GeneXpert MTB/RIF® for the diagnosis of pulmonary TB in an African settingAuthors: Philip Erik Wikman Jorgensen1,2,3, Jara Llenas-García2, Tomás María Pérez-Porcuna1, Alejandra Morales4, Michael Hobbins5, Jochen Ehmer5, Rosa Abellana1 , Francisco Mbofana6 , Manuel Aly Mussa7, Carlos Ascaso1

1; University of Barcelona. Department of Public Health. Casanova,143, Barcelona 08036, Spain. 2; SolidarMed Mozambique. C.P: 357 Rúa das Finanças, Pemba. Cabo Del-gado. Mozambique. 3; San Juan de Alicante University Hospital, Infectious diseases department, Alicante, Spain. Internal Medicine Department, Hospital 12 de Octubre, Madrid. Spain. 4; SolidarMed Switzerland. Obergrundstrasse 97, 6000 Lucerne 4, Switzerland. 5; Mozambique National Health Institute, Ministry of Health, Maputo. Mozambique. 6; Provincial Health Directorate. Operational Research Nucleous of Pemba. Cabo Delgado. Mozambique. PD-544-30

For Health in Africa.

Nucleo de Investigação

Operacional de Pemba

Bibliography - WHO. Global Tuberculosis Report 2013. (2013) - Pantoja, A., Fitzpatrick, C., Vassall, A., Weyer, K. & Floyd, K. Xpert MTB/RIF for diagnosis of tuberculosis and

drug-resistant tuberculosis: a cost and affordability analysis. Eur. Respir. J. 708–720 (2013). doi:10.1183/09031936.00147912

- Caviedes, L., Lee, T. & Gilman, R. Rapid, efficient detection and drug susceptibility testing of Mycobacterium tu-berculosis in sputum by microscopic observation of broth cultures. J. Clin. Microbiol. 38, 1203–1208 (2000).

- Moore, D. A. J. et al. Microscopic Observation Drug Susceptibility Assay , a Rapid , Reliable Diagnostic Test for Multi- drug-Resistant Tuberculosis Suitable for Use in Resource-Poor Settings J. Clin. Microbiol. 42, 4432–4437 (2004).

- Reddy, K. P. et al. Microscopic observation drug susceptibility assay for tuberculosis screening before isoniazid preventive therapy in HIV-infected persons. Clin. Infect. Dis. 50, 988–96 (2010).

- WHO. Epidemiological Fact Sheet on HIV and AIDS Core data on epidemiology and response Mozambique. (2008). - Meyer-rath, G. et al. The Impact and Cost of Scaling up GeneXpert MTB / RIF in SouthAfrica. PLoS One 7, (2012). - WHO. Report of the Commission on Macroeconomics and Health. Macroeconomics and Health: Investing in

Health for Economic Development. (2001). www.solidarmed.ch