The Impact and Cost of Scaling up GeneXpert MTB/RIF in South Africa

We estimated the incremental cost and impact on diagnosis and treatment uptake of national rollout of Xpert MTB/RIF technology (Xpert) for the diagnosis of pulmonary TB above the cost of current guidelines for the years 2011 to 2016 in South Africa.We parameterised a population-level decision model with data from national-level TB databases (n = 199,511) and implementation studies. The model follows cohorts of TB suspects from diagnosis to treatment under current diagnostic guidelines or an algorithm that includes Xpert. Assumptions include the number of TB suspects, symptom prevalence of 5.5%, annual suspect growth rate of 10%, and 2010 public-sector salaries and drug and service delivery costs. Xpert test costs are based on data from an in-country pilot evaluation and assumptions about when global volumes allowing cartridge discounts will be reached.At full scale, Xpert will increase the number of TB cases diagnosed per year by 30%-37% and the number of MDR-TB cases diagnosed by 69%-71%. It will diagnose 81% of patients after the first visit, compared to 46% currently. The cost of TB diagnosis per suspect will increase by 55% to USD 60-61 and the cost of diagnosis and treatment per TB case treated by 8% to USD 797-873. The incremental capital cost of the Xpert scale-up will be USD 22 million and the incremental recurrent cost USD 287-316 million over six years.Xpert will increase both the number of TB cases diagnosed and treated and the cost of TB diagnosis. These results do not include savings due to reduced transmission of TB as a result of earlier diagnosis and treatment initiation

Model assumptions and sources.

<p>ETR 2010, Electronic TB Register 2010; NHLS 2010, National Health Laboratory Services database 2010; NDoH guidelines, South African National TB Guidelines <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036966#pone.0036966-National1" target="_blank">[13]</a>; QTBS 2010, Quarterly TB Statistics, National Department of Health 2010 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036966#pone.0036966-TB1" target="_blank">[12]</a>.</p>a<p>Two sputa.</p>b<p>The proportion smear positive amongst all patients, and the proportion culture positive amongst smear negative patients, decreases in both scenarios over time as a function of the growth in suspects, allowing us to model a stable epidemic.</p>c<p>Adjusted using weights by HIV and history status from ETR.</p>d<p>Smear negative, diagnosed by antibiotic trial and/or chest x-ray.</p

Diagnostic algorithm under current guidelines (Baseline scenario) and proposed new guidelines (Xpert scenario).

<p>LPA denotes line probe assay; DST, drug-susceptibility testing. Adult patients with suspected pulmonary MTB infection undergo a number of TB diagnostics at each of up to three consecutive diagnostic visits. Under the Baseline scenario, diagnostics are differentiated by whether or not patient have a history of TB treatment, and, for smear-negative patients, by HIV status. Under the Xpert algorithm, diagnostics are differentiated by HIV status for patients with a negative Xpert result only. Under both algorithms patients with a positive culture undergo further testing by line probe assay and, if this shows a resistance to RIF and/or INH, by drug-susceptibility testing for second line TB drugs. Under the Xpert scenario, patients with a positive Xpert result and RIF resistance (MTB+/RIF+) undergo further sputum microscopy and culture +/− LPA +/− DST for confirmation of the MDR-TB result and exclusion of XDR-TB. For smear microscopy, two sputa are collected; for an Xpert test, a single sputum is used. All tests are done on spot sputum samples.</p

Number of suspects and number of patients >15 years diagnosed with TB per year, by scenario.

a<p>Suspects with unknown HIV status are assumed to be HIV positive, in keeping with the South African TB guidelines <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036966#pone.0036966-Actuarial1" target="_blank">[15]</a>.</p>b<p>“Drug resistant TB” includes INH mono-resistance, RIF mono-resistance, and multi-drug resistance.</p

Total cost of diagnostic and treatment programme and cost per case and per suspect by scenario [2011 USD].

<p>Total cost of diagnostic and treatment programme and cost per case and per suspect by scenario [2011 USD].</p

Cost inputs in 2011 USD.

a<p>In an agreement between the manufacturer and the Foundation for Novel Diagnostics (FIND), the cost of Xpert cartridges for the public sector in 116 high-burden and all low- and middle-income countries has been set to USD 16.86 apiece for volumes of between 600,000 to 1.7 million globally turned-over cartridges, USD 14.00 between for volumes between 1,700,001 to 3,700,000, and USD 10.72 for volumes from 3,700,001 cartridges onwards <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036966#pone.0036966-World3" target="_blank">[14]</a>. The cost used here includes the cost of shipping to South Africa and local value-added tax.</p

Timing of diagnosis for patients with drug resistant TB.

<p>Percentage of patients with drug-resistant TB diagnosed by visit 2 (assumed 5 days after first visit), by visit 3 (assumed 4–6 weeks after first visit), and thereafter (accelerated scale-up, 10% growth in suspects).</p

Timing of diagnosis for all patients.

<p>Percentage of all patients diagnosed by visit 2 (assumed 5 days after first visit), by visit 3 (assumed 4–6 weeks after first visit), and thereafter (accelerated scale-up, 10% growth in suspects).</p

Treatment algorithm by resistance status.

<p>R denotes rifampicin, H, isoniazid, Z, pyrazinamide, E, ethambutol, S, streptomycin, OFX, ofloxacin, KM, kanamycin, ETO, ethionamide, PZA, pyrazinamide, TRD, terizidone. Patients diagnosed with pulmonary TB are initiated on TB treatment according to their drug resistance status and, for the Baseline scenario, by their TB history. In the Xpert scenario, all patients without resistance are treated as New cases; regimen 2 is no longer used.</p