Gone are the days when diagnosis of a disease like cancer or tuberculosis would remain elusive for months or years together. Gone are the days when clinicians would keep speculating about the causes of a fever with no specific diagnosis. Gone are the days when the only modality available to diagnose a disease was a battery of routine blood tests and there was no way for a clinician to find out the changes occurring at a cellular and sub cellular level. Gone are the days when drugs would be given to patients without really finding out beforehand, whether or not the drug would really work on the patient. Gone are the days when the patient would have to go all the way to a pathology centre merely for checking blood glucose.
| Dr Arnab Roy |
The advancements in the field of medical diagnostics have revolutionised the entire gamut of detecting and identifying diseases. The concept of monitoring the efficacy of a therapeutic regimen through monitoring tests has got assimilated in mainstream clinical practice. Patients are not just tested any more to merely diagnose diseases but also undergo diagnostic tests, for determining the best suited therapy for each one of them. Besides, point-of-care testing devices like glucometers and pregnancy urine kits among many others have transposed diagnostics from the laboratory, to the site of care of the patient. Indeed, in the past few decades, the arena of diagnostics has grown from strength to strength. This progress in medical diagnostics has made it possible to achieve milestones in the realms of personalised medicine, gene therapy, molecular pathology, companion diagnostics and point-of-care testing. However, Rome was not built in a day!! Several years of relentless research and upgradation has gone into this change. Thus, on the occasion of World Health Day, it seems apt to take a trip down memory lane and look back at the journey of medical diagnostics.
| Dr Faisal Khan |
With the passage of time, the horizon of diagnostic modalities has widened from simple smear microscopy, histopathological examination and pathogenic culture to serological assays, biochemical analysis, molecular pathology, monoclonal antibody mediated techniques and a wide array of PCR based methods; the change has been phenomenal. To better identify as to how the emergence of newer diagnostic techniques influences the patterns of disease detection; let’s consider the case of a few interesting disease areas. To begin with, let’s have a look at the changes that have been witnessed in the diagnosis of TB. In the late 18th century, Robert Koch identified Mycobacterium Tuberculosis, stained this causative pathogen and visualised it under a microscope. In effect, this was one of the earliest applications of what later came to be known as ‘smear microscopy.’ This remained a widely used method in the diagnosis of TB for a long period of time. However, the acceptance of smear microscopy plummeted as several sputum-smear negative TB cases went undiagnosed and got reported as false negatives. This presented an unmet medical need for a more robust diagnostic option: A need that was satisfied by performing a pathogenic culture of Mycobacterium Tuberculosis; which remains the gold standard hitherto. In due course of time, serological tests also received wide acceptance as an adjunctive modality in the diagnosis of TB. However, in lieu of mounting evidence confirming misdiagnosis of TB with serological tests, regulatory authorities and international medical bodies issued recommendations banning the use of serological assays for TB diagnosis. The most noteworthy development in the area of TB diagnosis has in fact taken place in the recent past, with the introduction of a real time PCR based, US-FDA approved and WHO endorsed molecular assay called Xpert MTB/RIF. This molecular diagnostic method has substantially changed the paradigm of TB diagnostics in the last decade. As compared to the gold standard; it is quicker, has fewer infrastructural pre-requisites, is less technique sensitive and is highly automated which significantly marginalises the possibility of human error. Its diagnostic accuracy is comparable to the gold standard. It can be effectively employed for confirmatory diagnosis of pulmonary, extra-pulmonary, paediatric and MDR forms of TB as well as HIV-TB co-infections.
A similar progression in diagnostic techniques can be traced by taking another example from oncology, that of acute myeloid leukaemia (AML). Traditionally, peripheral blood smears were examined to validate a presumptive diagnosis of AML by visualising leukaemic blast cells. Subsequently, this primary diagnostic method was followed by bone marrow aspiration smears for confirmatory diagnosis; which hold true even today. In addition to this, flow cytometry techniques have been developed which detect the presence of several tumour markers in the blood sample of an AML patient. This technique is now widely employed in the diagnostic work up of AML not only for confirmatory diagnosis; but also for distinguishing between AML and acute lymphoid leukaemia and other lymphoproliferative disorders. Moreover, cytogenetics has identified a fusion gene called PML/RARa which has been recognised as the genetic signature of the disease and another fusion transcript AML/ETO which can help prognosticate a case of AML. In addition to the traditionally employed smears used for primary and confirmatory diagnosis, PCR based biomarker tests can detect tumour markers like FLT3, NPM1, CEBP-a and WT1. These tumour markers provide critical insight in predicting the prognosis of AML and have been recommended by international guidelines.
The examples of TB and AML that have been presented here to cite the advancements in the realm of diagnostics perhaps depict just the tip of the iceberg. A plethora of such other examples can be cited which would speak volumes about the changing landscape of diagnosis and its impact on disease intervention, therapy decision making and clinical outcomes. However, including multiple such examples is beyond the scope of this write up. Nevertheless, it would be useful to throw light at least upon one more crucial disease area; wherein diagnostics seem to have literally gone from bench to bedside. Of course, we are pointing towards diabetes, as a disease segment and the vast range of point of care testing (POCT) products for diabetes. Glycated haemoglobin can be measured with rapid automated POCT instruments for long term monitoring of blood glucose. Urinalysis dipsticks and blood betahydroxybutyrate meters are widely used for measuring ketones in blood and urine. Semi-quantitative visual dipsticks and quantitative automated methods of urine testing became are freely available for bedside detection of urinary albumin at low concentrations and for the determination of the microalbumin creatinine ratio. This wide range of POCT products has gone a long way in easing the lives of diabetics for whom continuous serial monitoring is needed. Besides, POCT measures also ensure rapid and quick diagnosis, better patient compliance and reduce repetitive visits to a reference laboratory. POC diagnostic products are also widely popular in the measurements of electrolytes, blood gases and coagulation markers.
Medical diagnostics is set to undergo a significant metamorphosis as the wheel of time continues to spin. The situation is thus pregnant with new avenues and vistas in diagnostics, which can result in remarkable changes in the detection, diagnosis and management of diseases in times to come. The vast body of scientific knowledge obtained through the study of the human genome and functional genomics has led to the discovery and clinical validation of a plethora of diagnostic biomarkers. These biomarkers are being employed in screening, primary diagnosis, therapy decision making, therapeutic monitoring and prognostication. Biomarkers, as well as gene targeted therapy, represent the combined new frontier of laboratory medicine as well as of clinical management. Diagnostic algorithms assisted by computerised technology have enabled the assessment of large panels of molecular targets of a disease rather than testing individual biomarkers. Furthermore, the concept of bringing diagnostics to the bedside of the patient has gone a long way in easing patient care by accelerating treatment decisions and reducing costs. In the recent past, one of the key concerns of the healthcare sector has been increasing healthcare costs. However, under the umbrella of health care services, ‘diagnostics’ perhaps is the only segment that continues to remain the most cost efficient one. The demand supply equation is expected to further tilt in favour of the diagnostics domain as the demand for more and more rapid laboratory medicine services, increases within clinical practice. At this notable turning point, when the diagnostics industry is experiencing the flux of change and growth, the key to sustainable development lies in coaching and mentoring the next generation of laboratorians into seasoned lab professionals.
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