There is no doubt that research and development of new diagnostic technologies and effective drugs must go ahead with full thrust. But there is no single 'magic wand' intervention and therefore deploying existing diagnostic tools optimally and managing treatment well are no less a priority to reach the formidable tuberculosis (TB) related goal of zero new infections, deaths and suffering.
There is no doubt how important it is for public health to find a TB case as early as possible, to get a confirmed and accurate laboratory based diagnosis of the disease done and successfully complete treatment and care. But are new state-of-the-art diagnostic tools in the market really helping in finding a TB case early on? Theoretically if we diagnose a TB case earlier the person should be able to receive standard treatment earlier than usual too. But realistically other ‘influencers’ factor in making it very clear that merely getting a new technology or tool alone will not become a ‘magic bullet’ but how we deploy it and programme it will get us the desired outcomes.
Dr Pren Naidoo from South Africa evaluated whether deployment of new rapid diagnostic tools such as GeneXpert MTB/RIF has made a real difference in Cape Town, South Africa, in terms of increasing TB and multidrug-resistant TB (MDR-TB) screening, case detection of TB and MDR-TB, reduction of time duration between getting a confirmed accurate diagnosis and initiation of treatment, and cost effectiveness, among other study objectives.
Cape Town had reported 28658 cases of TB and 953 MDR-TB cases in 2011. Hain's Line Probe Assay (LPA) was available in Cape Town since 2008 to provide drug-susceptibility testing (DST) and confirmed diagnosis for smear positive MDR-TB cases. GeneXpert MTB/RIF was introduced in Cape Town in 2011 in a phased manner across 8 sub-districts.
Dr Naidoo’s team conducted a study called ‘PROVE-IT’ to assess the impact of new TB molecular diagnostic tests within a routine operational setting at primary healthcare facilities in Cape Town. Contrary to earlier projections that introduction of new TB diagnostic technologies will get 30% higher case detection, number of presumptive TB cases that were screened in 8 sub-districts of Cape Town remained the same. Number of new TB cases diagnosed also did not increase across the region in Cape Town despite introduction of state-of-the-art diagnostic tool in 8 sub-districts.
Let’s look at the data: 188 MDR-TB cases were diagnosed in last quarter of 2010, and 196 MDR-TB cases have been diagnosed in second quarter of 2013. So there was no significant difference in number of MDR-TB cases getting diagnosed after introduction of GeneXpert MTB/RIF in 2011 onwards in this study setting.
Another important data to look at was whether introduction of GeneXpert MTB/RIF since 2011 in Cape Town has made a difference in reducing the time duration between getting a confirmed diagnosis for MDR-TB and getting initiated on standard treatment. This is where GeneXpert MTB/RIF had indeed made a positive difference by reducing the time duration from 43 to 17 days. But this is still a cause of serious concern because patients of MDR-TB get diagnosed in 90 minutes but have to wait for another 17 days to be put on treatment. This time delay has to be nipped.
Difference in cost per test between different TB diagnostic technologies was not significant too in Cape Town: Smear (bleach) costs USD 2.03; smear (NALC) & MGIT culture costs USD 9.01 (add USD 1.46 for positive culture), LPA costs USD 15.53, and GeneXpert MTB/RIF costs USD 18.31.
Dr Naidoo concluded with a question to the audience: Would we get better outcomes if GeneXpert MTB/RIF in Cape Town were placed in sites where culture and LPA were not available? A point-of-care (POC) HIV test costs USD 1 and that is what we should be thinking for TB and drug-resistant TB too, said Dr Naidoo.
Dr Madhukar Pai, Associate Director, McGill International TB Centre, argued that POC should be a test that not only diagnoses a patient quickly but also helps put the patient on treatment right then. POC is not a dipstick rather how a technology is used so that patients go with a clear treatment management plan. What matters is how we deploy a technology, said Dr Pai.
Dr Madhukar Pai said that mathematical models suggest if there was a sufficient roll-out of GeneXpert MTB/RIF then there will be some impact. “Diagnosis is just the start. When and what treatment is given after confirmed and accurate TB diagnosis and how it is managed has a much greater impact,” said Dr Pai. Dr Pai advocated that next study of the WHO should look at impact and not feasibility of new diagnostic technologies such as GeneXpert MTB/RIF.
Presently GeneXpert MTB/RIF is unlikely to reach the level of designated microscopy centres (DMCs) where much of TB testing is currently happening. GeneXpert MTB/RIF is mostly not being used in POC testing programmes to make treatment decisions in the same visit or the same day. GeneXpert MTB/RIF is also not accessible or affordable to first contact providers (informal/ private) who often see patients first and could shorten diagnostic delays.
Dr Pai stressed that impact of GeneXpert MTB/RIF should be maximized by optimizing algorithms and deployment strategies. Several products are under development but newer nucleic Acid Amplification Tests (NAATs) closer to the market, need to rapidly evaluate and generate evidence for policy review. In the longer term, we need biomarker-based triage and non-sputum based rapid tests, said Dr Pai.
Janet Ginnard of UNITAID said that there is a growing body of evidence for using GeneXpert MTB/RIF in diagnosing extrapulmonary TB (EPTB) and childhood TB. Janet shared how GeneXpert MTB/RIF cartridges are being procured under concessional pricing vs established number of smears. In a more competitive market, GeneXpert is unlikely to serve entire market segment, said Ginnard.
This correspondent had visited a GeneXpert MTB/RIF installed in a DOTS clinic in Yangon, Myanmar in September 2013. UNITAID's support in this direction is indeed helping diagnose MDR-TB cases earlier in the same visit. But treatment initiation may take months due to 'waiting list' issues as reported then. We risk losing the gains made by judicious deployment of new technologies in fight against TB if other components that make a TB programme work successfully does not get strengthened.
Bobby Ramakant, Citizen News Service - CNS
(The author is supported by the Global Alliance for TB Drug Development (TB Alliance) to provide conference coverage from the 44th Union World Conference on Lung Health)