Accuracy of rapid point-of-care serological tests for leprosy diagnosis: a systematic review and meta-analysis

Abstract

BACKGROUND Leprosy is a chronic infectious disease, still endemic in many countries that may lead to neurological, ophthalmic, and motor sequelae if not treated early. Access to timely diagnosis and multidrug therapy (MDT) remains a crucial element in the World Health Organization’s strategy to eliminate the disease as a public health problem. OBJECTIVES This systematic review aims to evaluate the accuracy of rapid point-of-care (POC) tests for diagnosis of leprosy. METHODS Searches were carried out in electronic databases (PubMed, EMBASE, CRD, Cochrane Library and LILACS) in April 2021 for patients with suspicion or confirmatory diagnostic of leprosy, classified in multibacillary (MB) or paucibacillary (PB) cases, performing rapid POC serological tests compared to clinical evaluation, smear microscopy and immunohistochemistry analysis. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). A meta-analysis was undertaken to generate pooled estimates of diagnostic parameters, presenting sensitivity, specificity and diagnostic odds ratio (DOR) values. The review protocol was registered at PROSPERO, CRD # 42014009658. FINDINGS From 893 potentially relevant references, 12 articles were included reporting 16 diagnostic tests accuracy studies with 5395 individuals enrolled. Meta-analysis of NDO-LID and PGL-I tests data in MB patients showed sensitivity and specificity [95% confidence interval (CI)] of 0.83 (0.71-0.91), 0.91 (0.72-0.97); and 0.92 (0.86-0.96), 0.93 (0.78-0.98); respectively, with high heterogeneity among the studies. MAIN CONCLUSIONS Our results can inform policymakers regarding the possibility of implementing accurate, rapid POC tests for leprosy in public health services, especially within primary health care.

Challenges and advances in serological and molecular tests to aid leprosy diagnosis

“…PGL-I serology mainly based on ELISA to detect IgM antibodies has been evaluated in several endemic countries throughout the world. 23,39,40 In general, these studies showed that anti-PGL-I positivity reflects the bacillary load: most MB patients are seropositive, while the majority of PB patients are seronegative. 38,41 Despite the limited application of anti-PGL-I serology for the diagnosis of all clinical forms of leprosy, it has been considered as an important adjunct tool for the operational classification of PB and MB leprosy.…”

“…For leprosy control programs, the incorporation of POCTs, such as the lateral flow rapid test, in alignment with bacilloscopy and qPCR, has the potential to help the decentralization of leprosy diagnosis, early diagnosis before the appearance of disabilities, and contact tracing of newly diagnosed patients, potentially contributing to interrupt M. leprae transmission chain. 23 However, POCT is not recommended as a standalone diagnostic test, but as an adjunct for bacilloscopy and for the referral of suspected cases to a reference center. 24 This review summarizes the state of the art of serological tests to aid the diagnosis of leprosy, highlighting the enzymelinked immunosorbent assay (ELISA) and POCT biotechnologies using the phenolic glycolipid-I (PGL-I) antigen and the impact of the postgenomic era on the production of new specific M. leprae antigens, such as the leprosy Infectious Disease Research Institute (IDRI) diagnostic-1 (LID-1).…”

“…Compared to ELISA to PGL-I and to LID-1, ELISA to NDO-BSA showed better overall performance in terms of sensitivity, specificity, positive and negative predictive values, and diagnostic odds ratio Gurung et al 20 Diagnostic accuracy of tests for leprosy: a systematic review and meta-analysis Despite reasonable accuracy of the tests, studies presented significant heterogeneity (thresholds, target antigens) and low methodological quality; therefore, the authors did not recommend the use of these tests for leprosy diagnosis as patients included in the studies evaluated were not representative of the patients who will receive these tests in the field de Oliveira et al 59 Diagnostic accuracy of tests using recombinant protein antigens of Mycobacterium leprae for leprosy: a systematic review Studies utilizing the ND-O-LID antigen have demonstrated enhanced accuracy in identify new leprosy cases among people living in endemic or non-endemic areas and household contacts in Brazil, Colombia, and the Philippines, especially when combined with other biomarkers Pierneef et al 78 Detection of anti-M. leprae antibodies in children in leprosy-endemic areas: a systematic review Quantitative a-PGL-I serology in young children holds promise as a screening test to assess M. leprae infection and may be applied as a proxy for transmission and thereby as a means to monitor the effect of (prophylactic) interventions on the route to leprosy elimination Romero et al 23 Accuracy of rapid point-of-care serological tests for leprosy diagnosis: a systematic review and meta-analysis…”

“…A recent systematic review and meta-analysis on rapid point-of-care serological tests for leprosy diagnosis reported that although the accuracy results were not conclusive, they showed that PGL-I tests performed better than the NDO-LID tests, both in terms of sensitivity and specificity; however, a high degree of heterogeneity was observed in studies for both tests (Table 1). 23 The Leprosy POCT ML Flow test has been recently approved by the Brazilian Public Health System (SUS) and by the Leprosy Control Program to be used only for contact surveillance and is currently being implemented throughout the country; however, the impact of this intervention in leprosy transmission requires time and evaluation. 73 This decision has been followed by academic technology transfer of ML Flow production protocols (SBS, UFG, Brazil) to a private industry (Bioclin, MG, Brazil) assuring large-scale, quality-controlled production of tests for public health use.…”

Advances in the Diagnosis of Leprosy

“…In this review, we have tried to compile all the information available in the literature regarding the recent developments for leprosy diagnosis (Table 1). We refer readers to other reviews to know about the recent advancements in biomarker-based research for leprosy detection (65)(66)(67)(68) and meta-analysis for sensitivity and specificity studies of laboratory tests (10,(29)(30)(31).…”