Rapid Quantitative Serological Test for Detection of Infection with Mycobacterium leprae, the Causative Agent of Leprosy

Abstract

Leprosy remains an important health problem in a number of regions. Early detection of infection, followed by effective treatment, is critical to reduce disease progression. New sensitive and specific tools for early detection of infection will be a critical component of an effective leprosy elimination campaign. Diagnosis is made by recognizing clinical signs and symptoms, but few clinicians are able to confidently identify these. Simple tests to facilitate referral to leprosy experts are not widely available, and the correct diagnosis of leprosy is often delayed. In this report, we evaluate the performance of a new leprosy serological test (NDO-LID). As expected, the test readily detected clinically confirmed samples from patients with multibacillary (MB) leprosy, and the rate of positive results declined with bacterial burden. NDO-LID detected larger proportions of MB and paucibacillary (PB) leprosy than the alternative, the Standard Diagnostics leprosy test (87.0% versus 81.7% and 32.3% versus 6.5%, respectively), while also demonstrating improved specificity (97.4% versus 90.4%). Coupled with a new cell phone-based test reader platform (Smart Reader), the NDO-LID test provided consistent, objective test interpretation that could facilitate wider use in nonspecialized settings. In addition, results obtained from sera at the time of diagnosis, versus at the end of treatment, indicated that the quantifiable nature of this system can also be used to monitor treatment efficacy. Taken together, these data indicate that the NDO-LID/Smart Reader system can assist in the diagnosis and monitoring of MB leprosy and can detect a significant number of earlier-stage infections. Despite advances toward the elimination of leprosy over the last 2 decades, new case detection rates have stabilized over the last decade and leprosy remains an important health problem in many regions (1). Like the number of registered cases, however, the number of clinicians who can reliably diagnose leprosy has waned, and delays in determining the correct diagnosis are common (2, 3). Efforts to develop and improve surveillance and referral systems appear necessary to achieve the early detection required to ensure that prompt and appropriate treatment can be provided to limit disabilities. The development of simple and practical tools to facilitate diagnosis would appear prudent.Currently, the diagnosis of leprosy is dependent on the appearance and recognition of clinical signs and symptoms. When skinsmear or pathology services are available, leprologists utilize the Ridley-Jopling scale to characterize five forms of the disease (4, 5). In practice, however, most field programs lack such services, and the clinical system suggested by WHO to classify individual patients and to select their treatment regimen is used (6). The WHO system uses skin lesions, bacterial positivity by skin smear, and the number of involved nerves to group leprosy patients into one of two simplified categories: multibacillary (MB) leprosy (patients are typically smear pos...

Identification of Antibody Targets for Tuberculosis Serology using High-Density Nucleic Acid Programmable Protein Arrays

“…We thus anticipate that the NAPPA-based identified candidate antigens, if validated in larger studies in diverse TB endemic regions, could contribute to the generation of simple lateral-flow tests. Such simple tests exist already for the diagnosis of other complex and difficult to diagnose infectious diseases such as leprosy or crytococcosis (48,49). Such simple tests could further be evaluated as screening tools as well as in combination with other diagnostic methods, especially in those groups that are particularly challenging to diagnose, such as HIV coinfected and/or extrapulmonary TB patients, patients with insipient or culture-negative TB, or pediatric TB patients (50 -54).…”

Integrative literature review of the reported uses of serological tests in leprosy management

“…In particular, the estimated risk of developing multibacillary leprosy is 34.4 times higher when antibodies against PGL-I are detected (33) . Similarly, evaluation of IgM and immunoglobulin G (IgG) antibodies against the NDO-LID conjugate allows detection of a significant number of M. leprae-infected individuals in early stages of disease development (29) . Further, accurate measurement of antibody titers may also be useful, because increased titers of anti-PGL-I (NDO-BSA) and anti-LID-1 could potentially identify household contacts that require careful monitoring or clinical examination (35) ( Table 2).…”

“…The possibility and feasibility of carrying out large-scale screening campaigns to detect antibodies against PGL-I, LID-1, and NDO-LID should therefore be investigated as a means to identify M. leprae-infected individuals (5) . Regular and sustained monitoring of suspected cases is also suggested (29) . Since successive evaluation of antibodies may contribute to early diagnosis, rapid tests based on PGL-I, LID-1, and NDO-LID antigens should be incorporated into primary health care services in order to detect household contacts and other individuals at risk of becoming sick.…”

“…In addition, detection of antibodies against recombinantly expressed M. leprae proteins enhances PGL-I-based identification of household contacts at greater risk of developing leprosy (40) ( Table 2). Indeed, the LID-1 antigen may be used as a screening tool (41) , while evaluation of antibodies against NDO-LID can improve surveillance, facilitate referral to an expert (29) , and help develop new interventions and treatments.…”

“…Indeed, laboratory-based ELISA has been used to analyze seroreactivity against PGL-I (4) (5) (17) , LID-1 (4) (5) (17) , ML0405, ML2331 (4) (17) , and NDO-LID (5) (29) . On the other hand, ML Flow is a simple, fast (9) , and reliable tool to detect anti-PGL-I (10) using NTP as antigen, a semi-synthetic trisaccharide analog of PGL-I that is chemically linked to either bovine or human serum albumin (11) .…”