Polymerase Chain Reaction (PCR) as a Potential Point of Care Laboratory Test for Leprosy Diagnosis—A Systematic Review

Tatipally, Sushma; Srikantam, Aparna; Kasetty, Sanjay

doi:10.3390/tropicalmed3040107

Cited by 29 publications

(32 citation statements)

References 44 publications

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“…The routine practice after introduction of qPCR was effective in our clinic. Indeed, a systematic review and meta-analysis indicates that PCR has good accuracy, although studies are highly heterogeneous suggesting that large multicentric studies using good manufacturing practices products for diagnostic purposes should be used for validation of the present data 29 .…”

Section: Discussionmentioning

confidence: 83%

Leprosy incidence and risk estimates in a 33-year contact cohort of leprosy patients

Hacker

Sales

Duppré

et al. 2021

Sci Rep

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Reduction in incidence has been associated with the introduction of novel approaches, like chemo/immune-prophylaxis. Incidence determined through follow-up cohort studies can evaluate the implementation of these innovative policies towards control and prevention. We have assessed the incidence in our contacts cohort over past 33 years, considering the effect of demographic and clinical variables. Survival analysis was used to estimate the risk of leprosy. A total of 9024 contacts were evaluated, of which 192 developed leprosy, resulting in an overall incidence of 1.4/1000 person-years. The multivariate analysis showed that the major risk factors were (i) contact from MB index cases and (ii) consanguinity (iii) intra household contact. Lower risk was detected for contacts with BCG scar who were revaccinated. There was a significant decrease in accumulated risk between the 2011–2019 period compared with 1987, probably linked to the improvement in laboratory tools to monitor contacts, thereby providing early diagnosis of contacts at intake and reduction of transmission. Our findings suggest that a combination of contact surveillance and tracing, adequate neurodermatological examination, and availability of molecular tools is highly effective in supporting early diagnosis, while a second dose of the BCG vaccination can exert extra protection.

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Section: Discussionmentioning

confidence: 83%

Leprosy incidence and risk estimates in a 33-year contact cohort of leprosy patients

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Sales

Duppré

et al. 2021

Sci Rep

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“…While other genes ( 16SrRNA , esxA , Ag85B , sodA , pra , rpoT , ML2179 , ML1545 , ML0098 , ML0024 , MntH , AT repeats , AGT repeats , TTC repeats ) with the sensitivity ranged from 20% to 94% in previous studies. [13–22,24–26,29] showed decreased sensitivities compared to RLEP and groEL in this study.…”

Section: Discussionmentioning

confidence: 44%

Development and evaluation of a droplet digital PCR assay for the diagnosis of paucibacillary leprosy in skin biopsy specimens

et al. 2019

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Background The reduced amounts of Mycobacterium leprae ( M . leprae ) among paucibacillary (PB) patients reflect the need to further optimize methods for leprosy diagnosis. An increasing number of reports have shown that droplet digital polymerase chain reaction (ddPCR) is a promising tool for diagnosis of infectious disease among samples with low copy number. To date, no publications have investigated the utility of ddPCR in the detection of M . leprae . The aim of this study was to develop and evaluate a ddPCR assay for the diagnosis of PB leprosy. Methodology The two most sensitive DNA targets for detection of M . leprae were selected from electronic databases for assessment of sensitivity and specificity by quantitative polymerase chain reaction (qPCR) and ddPCR. Control patients (n = 59) suffering from other dermatological diseases were used to define the cut-off of the duplex ddPCR assay. For comparative evaluation, qPCR and ddPCR assays were performed in 44 PB patients and 68 multibacillary (MB) patients. Principal findings M . leprae -specific repetitive element ( RLEP ) and groEL (encoding the 65 kDa molecular chaperone GroEL) were used to develop the ddPCR assay by systematically analyzing specificity and sensitivity. Based on the defined cut-off value, the ddPCR assay showed greater sensitivity in detecting M . leprae DNA in PB patients compared with qPCR (79.5% vs 36.4%), while both assays have a 100% sensitivity in MB patients. Conclusions/Significance We developed and evaluated a duplex ddPCR assay for leprosy diagnosis in skin biopsy samples from leprosy patients. While still costly, ddPCR might be a promising diagnostic tool for detection of PB leprosy.

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“…The sensitivity of RLEP PCR is reported to be 57%-80% for the diagnosis of leprosy. When evaluated using clinical specimens, AFB positivity in skin biopsy was 44% (range 10–85), whereas PCR positivity in skin biopsy was 70% (range 46–93) [27]. When comparing different PCR methods, the highest percentage of PCR sensitivity was observed using the multiplex PCR technique (82%), followed by RT-PCR (78%) and conventional PCR (63%) [27].…”

Section: Discussionmentioning

confidence: 99%

“…When evaluated using clinical specimens, AFB positivity in skin biopsy was 44% (range 10–85), whereas PCR positivity in skin biopsy was 70% (range 46–93) [27]. When comparing different PCR methods, the highest percentage of PCR sensitivity was observed using the multiplex PCR technique (82%), followed by RT-PCR (78%) and conventional PCR (63%) [27]. We observed a sensitivity of 58.57%-91.42% for FFPE from MB patients and 17.39%-39.13% for FFPE from PB patients but better specificity (100%) with the STNPCR and SYBRGreen primers.…”

Section: Discussionmentioning

confidence: 99%

“…We observed a sensitivity of 58.57%-91.42% for FFPE from MB patients and 17.39%-39.13% for FFPE from PB patients but better specificity (100%) with the STNPCR and SYBRGreen primers. Because skin biopsy is the most frequent clinical procedure used to collect samples for leprosy diagnosis and RLEP is the most frequent marker used, suitable tools, such as RLEP PCR for FFPE specimens, for providing bacteriological evidence of leprosy are needed for early case detection and appropriate therapeutic management [27].…”

Section: Discussionmentioning

confidence: 99%

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Develop and Field Evolution of Single Tube Nested PCR, SYBRGreen PCR Methods, for the Diagnosis of Leprosy in Paraffin-embedded Formalin Fixed Tissues in Yunnan Province, a Hyper endemic Area of Leprosy in China

Chen

Xing

et al. 2019

PLoS Negl Trop Dis

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BackgroundDetection and pathology analysis of Mycobacterium leprae using skin biopsy tissues are essential for leprosy diagnosis and monitoring response to treatment. Although formalin fixation of patient tissues may not be ideal for molecular studies, biopsy samples are the most accessible material from suspected cases. Therefore, clinical molecular laboratories must be able to utilize formalin-fixed, paraffin-embedded (FFPE) material.ObjectiveTo determine the best molecular method for diagnosing and monitoring leprosy in FFPE specimens, we developed a single-tube nested PCR (STNPCR) (131 bp) and SYBRGreen PCR (101 bp) assay using primers for the M. leprae-specific repetitive element (RLEP) gene and evaluated the results compared to those using previously established RLEP primers (372 bp).MethodsFFPE biopsy samples obtained from 145 leprosy patients (during or after multidrug therapy (MDT)) and patients with 29 other confounding dermatoses were examined by the bacteria index (BI) and by simple PCR, STNPCR, and SYBRGreen PCR using primers amplifying a 372-bp, 131-bp or 101-bp fragment of RLEP, respectively.ResultsIn leprosy patients receiving MDT, STNPCR showed a highest specificity of 100% and a positive predictive value (PPV) of 100%. For multibacillary (MB), paucibacillary (PB) and all leprosy patients, the highest sensitivities were 91.42%, 39.13%, and 67.92%, negative predictive values (NPVs) were 8.57%, 60.36%, and 32.07%, and the highest accuracies were 93.93%, 62.67%, and 74.81%, respectively, higher than the results of SYBRGreen PCR and simple PCR. For post-MDT leprosy patients, SYBRGreen PCR showed the highest sensitivity of 50.0%, highest specificity of 100%, a PPV of 100%, an NPV of 100% and the highest accuracy of 83.72% for MB patients, which were higher than those of STNPCR and simple PCR. STNPCR showed the highest sensitivity of 26.66% and 34.48%, highest specificity of 100% and 100%, a PPV of 100% and 100%, NPV of 72.50% and 60.21%, and highest accuracy of 75.00% and 67.24% for PB and leprosy patients, respectively, higher than those of SYBRGreen PCR and simple PCR.ConclusionsThese findings suggest that STNPCR or SYBRGreen PCR (131-bp and 101-bp fragment amplification, respectively) for RLEP using FFPE specimens performs better as a diagnostic test and for monitoring response to MDT than does simple PCR based on 372-bp fragment amplification. Additionally, STNPCR showed increased sensitivity for PB diagnosis using FFPE specimens, which can be transferred remotely or retrieved from previous leprosy patients.

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Polymerase Chain Reaction (PCR) as a Potential Point of Care Laboratory Test for Leprosy Diagnosis—A Systematic Review

Cited by 29 publications

References 44 publications

Leprosy incidence and risk estimates in a 33-year contact cohort of leprosy patients

Leprosy incidence and risk estimates in a 33-year contact cohort of leprosy patients

Development and evaluation of a droplet digital PCR assay for the diagnosis of paucibacillary leprosy in skin biopsy specimens

Develop and Field Evolution of Single Tube Nested PCR, SYBRGreen PCR Methods, for the Diagnosis of Leprosy in Paraffin-embedded Formalin Fixed Tissues in Yunnan Province, a Hyper endemic Area of Leprosy in China

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