Comparative evaluation of antibody detection tests to facilitate the diagnosis of multibacillary leprosy.

Despite control efforts, leprosy persists as a significant health concern in many regions. Diagnosis is achieved by a combination of clinical, histopathological, and bacteriological examinations, each of which presents a barrier to expeditious diagnosis, particularly by non-experts. Immunological investigations in research laboratories have clearly indicated that antibody detection tests could aid the diagnosis of leprosy. In this study, we detected circulating antibodies with two rapid diagnostic tests (RDT) involving immunochromatographic lateral flow platforms and one rapid ELISA system. Leprosy patients were identified with a high degree of sensitivity in each assay (over 80% in all; over 90% among cases with bacterial indices >1+), although critical differences were observed in specificity. While the specificity of CTK OnSite Leprosy Ab Rapid Test and InBios Leprosy Detect™ fast ELISA were high (96.4 and 93.7% in the general population, respectively), there was a marked reduction in OrangeLife NDO-LID® RDT (only 25.0%). As anticipated, seropositivity rates were marginally higher in contacts of leprosy patients than in endemic controls. Although we observed a slight drop in test band intensity when blood, rather than serum, was used to develop OnSite Leprosy Ab Rapid Tests, the sensitivity and specificity of these tests was unaffected. When we contrasted test performance with clinical and bacteriological information, we found that RDT and ELISA results positively correlated with the bacteriological index. These data indicate that these assays could be a ready replacement of invasive, insensitive, and time consuming skin slit smear procedures that additionally require expert microscopic examinations. We propose that, due to their speed and point of care applicability, the RDT could be used as an initial entry point to the diagnostic protocols, with confirmation of results attained in a highly quantitative manner following serum transfer to a reference laboratory.

Development of a quantitative rapid diagnostic test for multibacillary leprosy using smart phone technology.

BACKGROUND: Despite efforts to eliminate leprosy as public health problem, delayed diagnosis and disabilities still occur in many countries. Leprosy diagnosis remains based on clinical manifestations and the number of clinicians with expertise in leprosy diagnosis is in decline. We have developed a new immunochromatographic test with the goal of producing a simple and rapid system that can be used, with a minimal amount of training, to provide an objective and consistent diagnosis of multibacillary leprosy. METHODS: The test immobilizes two antigens that have been recognized as excellent candidates for serologic diagnosis (the PGL-I mimetic, ND-O, and LID-1), on a nitrocellulose membrane. This allows the detection of specific IgM and IgG antibodies within 20 minutes of the addition of patient sera. Furthermore, we coupled the NDO-LID® rapid tests with a new cell phone-based test reader platform (Smart Reader®) to provide objective interpretation that was both quantifiable and consistent. RESULTS: Direct comparison of serologic responses indicated that the rapid test detected a greater proportion of leprosy patients than a lab-based PGL-I ELISA. While positive responses were detected by PGL-I ELISA in 83.3% of multibacillary patients and 15.4% of paucibacillary patients, these numbers were increased to 87% and 21.2%, respectively, when a combination of the NDO-LID® test and Smart Reader® was used. Among multibacillary leprosy the sensitivity of NDO-LID® test assessed by Smart Reader® was 87% (95% CI, 79.2-92.7%) and the specificity was 96.1% (95% CI, 91.7- 98.6%). The positive predictive value and the negative predictive value of NDO-LID® tests were 94% (95% CI, 87.4-97.8%) and 91.4% (95% CI, 85.9-95.2%), respectively. CONCLUSION: The widespread provision of rapid diagnostic tests to facilitate the diagnosis or prognosis of multibacillary leprosy could impact on leprosy control programs by aiding early detection, directing appropriate treatment and potentially interrupting Mycobacterium leprae transmission.

Comparison of two rapid tests for anti-phenolic glycolipid-I serology in Brazil and Nepal

The diagnosis of leprosy continues to be based on clinical symptoms and early diagnosis and treatment are critical to preventing disability and transmission. Sensitive and specific laboratory tests are not available for diagnosing leprosy. Despite the limited applicability of anti-phenolic glycolipid-I (PGL-I) serology for diagnosis, it has been suggested as an additional tool to classify leprosy patients (LPs) for treatment purposes. Two formats of rapid tests to detect anti-PGL-I antibodies [ML immunochromatography assay (ICA) and ML Flow] were compared in different groups, multibacillary patients, paucibacillary patients, household contacts and healthy controls in Brazil and Nepal. High ML Flow intra-test concordance was observed and low to moderate agreement between the results of ML ICA and ML Flow tests on the serum of LPs was observed. LPs were "seroclassified" according to the results of these tests and the seroclassification was compared to other currently used classification systems: the World Health Organization operational classification, the bacilloscopic index and the Ridley-Jopling classification. When analysing the usefulness of these tests in the operational classification of PB and MB leprosy for treatment and follow-up purposes, the ML Flow test was the best point-of-care test for subjects in Nepal and despite the need for sample dilution, the ML ICA test yielded better performance among Brazilian subjects. Our results identified possible ways to improve the performance of both tests.

Comparison of two rapid tests for anti-phenolic glycolipid-I serology in Brazil and Nepal.

The diagnosis of leprosy continues to be based on clinical symptoms and early diagnosis and treatment are critical to preventing disability and transmission. Sensitive and specific laboratory tests are not available for diagnosing leprosy. Despite the limited applicability of anti-phenolic glycolipid-I (PGL-I) serology for diagnosis, it has been suggested as an additional tool to classify leprosy patients (LPs) for treatment purposes. Two formats of rapid tests to detect anti-PGL-I antibodies [ML immunochromatography assay (ICA) and ML Flow] were compared in different groups, multibacillary patients, paucibacillary patients, household contacts and healthy controls in Brazil and Nepal. High ML Flow intra-test concordance was observed and low to moderate agreement between the results of ML ICA and ML Flow tests on the serum of LPs was observed. LPs were "seroclassified" according to the results of these tests and the seroclassification was compared to other currently used classification systems: the World Health Organization operational classification, the bacilloscopic index and the Ridley-Jopling classification. When analysing the usefulness of these tests in the operational classification of PB and MB leprosy for treatment and follow-up purposes, the ML Flow test was the best point-of-care test for subjects in Nepal and despite the need for sample dilution, the ML ICA test yielded better performance among Brazilian subjects. Our results identified possible ways to improve the performance of both tests.