Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy

Spencer, John S.; Duthie, Malcolm S.; Geluk, Annemieke; Balagon, Marivic; Kim, Hee Jin; Wheat, William H.; Chatterjee, Delphi; Jackson, Mary; Li, Wei; Kurihara, Jade; Maghanoy, Armi; Mallari, Irene; Saunderson, Paul; Brennan, Patrick J.; Dockrell, Hazel M.

doi:10.1590/s0074-02762012000900014

Cited by 57 publications

(53 citation statements)

References 26 publications

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“…The findings of a number of studies (92)(93)(94)(95) contributed to the development of this test, which is being produced by the Infectious Disease Research Institute (IDRI) in conjunction with OrangeLife Laboratories in Rio de Janeiro, Brazil (96). Those researchers are investigating whether this test could be potentially useful with family contacts (95). If effective, such a test could potentially address the crucial need for more sensitive diagnostic tools for case detection in HD control today (35).…”

Section: Future Directionsmentioning

confidence: 99%

Leprosy in the 21st Century

2015

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SUMMARY Despite significant improvements in leprosy (Hansen's disease) treatment and outlook for patients since the introduction of multidrug therapy (MDT) 3 decades ago, the global incidence remains high, and patients often have long-term complications associated with the disease. In this article, we discuss recent findings related to genetics, susceptibility, and disease reservoirs and the implications of these findings for Hansen's disease control and health outcomes for patients. We describe the continued difficulties associated with treatment of inflammatory episodes known as “leprosy reactions,” which cause much of the disability associated with the disease and can affect people for many years after MDT is complete. We also discuss some of the contemporary challenges for physicians and patients, including international and internal migration of people affected by the disease. We suggest some important areas of focus for future Hansen's disease research.

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Section: Future Directionsmentioning

confidence: 99%

Leprosy in the 21st Century

2015

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“…Because the NDO-LID/Smart Reader is simple and rapid (10 to 20 tests can be conducted by one individual in 30 min), their integration could simplify and enhance this type of monitoring. The duration of any household visit could be markedly reduced, and evaluations could potentially be made at a much greater fre- (24,27). The levels detected in ELISA that have triggered such attention are readily detected in the NDO-LID test (30).…”

Section: Figmentioning

confidence: 99%

“…By lab-based ELISA, we previously identified reductions in patient antigen-specific antibody responses during treatment (24,32). These subtle changes can be captured by the NDO-LID/Smart Reader combination.…”

Section: Figmentioning

confidence: 99%

“…To date, leprosy rapid diagnostic tests have comprised only PGL-I mimetics as the antigenic target (ML Flow test and Standard Diagnostics leprosy test [hereinafter called SD Leprosy], containing tri-or disaccharides NTP and NDO, respectively) (14-17). Using laboratory-based assays, our group and others have identified numerous native and recombinant proteins recognized by antibodies in MB leprosy patient serum (18)(19)(20)(21)(22)(23)(24)(25). One example is the chimeric fusion protein leprosy IDRI diagnostic 1 (LID-1), an antigen specifically recognized by sera from leprosy patients from geographically and ethnically diverse populations, with a direct correlation between seroreactivity and BI (18,(26)(27)(28).…”

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confidence: 99%

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

Duthie

Balagon²,

Maghanoy³

et al. 2014

J Clin Microbiol

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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...

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“…Fortunately, diagnoses are typically provided before physical disabilities develop, while treatment and education help prevent further infections in the community (39) . 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.…”

Section: Surveillance Of Household Contacts and At-risk Populationsmentioning

confidence: 99%

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

Fabri

Carvalho

Vieira

et al. 2016

Rev. Soc. Bras. Med. Trop.

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Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy

Abstract: Although leprosy is curable with drug treatment, the identification of biomarkers of infection

Cited by 57 publications

References 26 publications

Leprosy in the 21st Century

Leprosy in the 21st Century

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

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

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