Leprosy is an infectious disease caused by Mycobacterium leprae
and mainly affects skin, peripheral nerves, and eyes [1
]. Leprosy has long-term consequences on the structure and function of the peripheral nerves leading to disabilities in limbs, which impact on the socioeconomic well-being of the affected individuals [4
]. Despite three decades of effective treatment with multidrug therapy (MDT), leprosy persists as a public health problem in many regions of the world [5
]. Each year 300,000 people are newly diagnosed with leprosy worldwide; half are reported from India [6
]. Despite the World Health Organization (WHO) declaring the elimination of leprosy as a public health problem in the year 2000, new leprosy cases still continue to occur in India with an annual incidence of around 135,000 cases [7
]. There is evidence that many more patients still go undetected due to various reasons including social stigma attached to the disease, which hinders health-care-seeking behavior among affected persons [8
]. Hence it is imperative to widen the scope and accuracy of leprosy detection for early identification before the consequences of nerve damage have set in [9
]. The current standard diagnosis of leprosy is mostly based on clinical evaluation of patients, except in a few settings where the microscopy of slit skin smears (SSS) for acid-fast bacilli and/or histopathological examination (HPE) of skin biopsies are being used as additional tests [10
]. Clinical manifestations of leprosy are determined by patient immune responses to Mycobacterium leprae
. Leprosy patients are classified by the Ridley–Jopling classification on the basis of the morphology, type, and number of skin lesions, as well as nerve involvement supplemented by the bacterial index (BI) and histopathological examination. The Ridley–Jopling types are tuberculoid (TT), borderline tuberculoid (BT), borderline (BB), borderline lepromatous (BL), lepromatous leprosy (LL), pure neural (PN) and indeterminate (I) [11
The current operational classification of leprosy used by WHO is based on number of skin lesions; patients with less than five lesions are classified as paucibacillary (PB) and more than five as multibacillary (MB) leprosy. However, this classification, merely based on the number of lesions, may not always hold good for specific treatment strategies, as it has been frequently demonstrated that acid-fast bacilli (AFB) are present in cases clinically classified as PB. Such PB patients with active lesions may potentially be transmitting M. leprae
to their contacts unless they are treated appropriately [12
]. Hence there has been an emphasis on bringing back the laboratory diagnostic component into routine practice [13
]. The two traditional tests viz.
SSS and HPE of biopsies, though still holding well in terms of convenience of usage, have their own inherent limitations. SSS is relatively low in sensitivity and includes the risk of subjective errors of microscopic examination, whereas the HPE has the limitations of long turnaround time and technically demanding laboratory procedures [14
]. Hence it is very important to develop diagnostic strategies involving highly sensitive laboratory tests for early detection of leprosy. Suitable tools for providing bacteriological evidence of leprosy are needed for early case detection and appropriate therapeutic management of leprosy. Ideally these tools are applicable at all health care levels for effective control of leprosy.
Molecular diagnosis by nucleic acid amplification test (NAAT) is an emerging science in the clinical management of infectious diseases. Polymerase chain reaction (PCR) is one of the most popular NAAT currently being used for the diagnosis of infectious diseases [15
]. Routine clinical use of NAAT has been well established in tuberculosis and other mycobacterial diseases. NAAT has almost replaced the conventional lab diagnostic tests in TB and has become the most widely used test at all levels of health care [16
]. Such molecular diagnosis has not yet been practiced in the case of leprosy. PCR nevertheless has been popularly used for drug resistance testing and molecular typing of leprosy but never so far for the routine clinical diagnosis [17
]. Given the potential use of this very important test, there is a need for a scientific analysis of the effectiveness of PCR for lab diagnosis of leprosy in correlation with the current standards. This evidence is envisaged to help the formulation of better policies for diagnosis and treatment of leprosy. With this background, the present systematic review analysis has been conducted in order to investigate the performance of PCR vis-à-vis SSS in various clinical settings and its potential usefulness as a routine lab test for leprosy diagnosis.