Who Expert Committee on Leprosy

Leprosy is a neglected infectious disease caused by acid-fast bacillus Mycobacterium leprae. It primarily affects the skin and then progresses to a secondary stage, causing peripheral neuropathy with potential long-term disability along with stigma. Leprosy patients account for a significant proportion of the global disease burden. Previous efforts to improve diagnostic and therapeutic techniques have focused on leprosy in adults, whereas childhood leprosy has been relatively neglected. This review aims to update the diagnostic and therapeutic recommendations for adult and childhood leprosy. This review summarizes the clinical, bacteriological, and immunological approaches used in the diagnosis of leprosy. As strategies for the diagnosis and management of leprosy continue to develop better and more advanced knowledge, control and prevention of leprosy are crucial.

/pdf/leprosy-a-review-of-epidemiology-clinical-diagnosis-and-2syftpmj.pdf

Leprosy: A Review of Epidemiology, Clinical Diagnosis, and Management

The diagnosis of cutaneous mycobacterial infections may be challenging. Owing to the broad spectrum of their clinical presentations, mycobacterioses have to be considered as differential diagnoses to many inflammatory dermatoses. Diagnostic measures comprise histology including special staining, cultures and molecular microbiological examinations as well as the detection of cellular immune reactions of the patient by means of interferon-γ release assays and skin testing. Clinicians should know the appropriate use and combination of procedures to diagnose mycobacterioses quickly and correctly and to avoid costs and delays caused by unnecessary examinations. This mini review summarizes advantages, limitations, and pitfalls of diagnostic methods for mycobacterial skin infections.

Diagnosis of mycobacterial skin infections

True incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. Diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3–10 years to manifest. The fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. This is supported by a high incidence of childhood leprosy. Epidemiological screening for pre-symptomatic leprosy in large endemic populations is required to facilitate targeted chemoprophylactic interventions. Such a test must be sensitive, specific, simple to administer, cost-effective, and easy to interpret. The intradermal skin test method that measures cell-mediated immunity was explored as the best option. Prior knowledge on skin testing of healthy subjects and leprosy patients with whole or partially fractionated Mycobacterium leprae bacilli, such as Lepromin or the Rees' or Convit' antigens, has established an acceptable safety and potency profile of these antigens. These data, along with immunoreactivity data, laid the foundation for two new leprosy skin test antigens, MLSA-LAM (M. leprae soluble antigen devoid of mycobacterial lipoglycans, primarily lipoarabinomannan) and MLCwA (M. leprae cell wall antigens). In the absence of commercial interest, the challenge was to develop these antigens under current good manufacturing practices in an acceptable local pilot facility and submit an Investigational New Drug to the Food and Drug Administration to allow a first-in-human phase I clinical trial.

/pdf/the-challenge-of-producing-skin-test-antigens-with-minimal-2ywdadv3bs.pdf

The challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.

Kutane Mykobakteriosen sind in Deutschland selten. Dennoch ist es fur eine fruhzeitige Diagnose und anschliesende wirksame Behandlung erforderlich, dass diese Krankheitsbilder im arztlichen Bewusstsein verankert sind. Daruber hinaus stehen Infektionen mit Mykobakterien auf der Liste der Differentialdiagnosen vieler Hautkrankheiten. Diagnosen kutaner Mykobakteriosen beruhen auf klinischen Merkmalen und auf Laboruntersuchungen, einschlieslich bakterieller Kulturen, histopathologischer Untersuchungen und PCR-basierten Verfahren. Das Wissen um Moglichkeiten und Grenzen dieser Laboruntersuchungen ist von zentraler Bedeutung, um eine angemessene klinische Entscheidung zu treffen. In diesem Beitrag diskutieren wir die aktuellen diagnostischen Moglichkeiten, die in Verdachtsfallen kutaner Mykobakteriosen zur Verfugung stehen.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ddg.13001_g

Keim oder kein Keim: Herausforderungen bei der Diagnose mykobakterieller Infektionen der Haut.

Background: New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials. Methods: A Phase I safety trial was first conducted in a non-endemic region for leprosy (U.S.A.). Healthy non-exposed subjects (n=10) received three titrated doses (2.5 mg, 1.0 mg and 0.1 mg) of MLSA-LAM (n=5) or MLCwA (n=5) and control antigens [Rees MLSA (1.0 mg) and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal), but involved only the 1.0 mg (high dose) and 0.1 mg (low dose) of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose), each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients, 20 household contacts of leprosy patients (HC), and 20 tuberculosis (TB) patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration. Findings: In the small Phase I safety trial, reactions were primarily against the 2.5 mg dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50) showed induration against the high dose of each antigen, and 4% (2 of 50) reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens showed lower specificity (70% and 60%) and sensitivity (10% and 15%). BL/LL leprosy patients were anergic to the leprosy antigens. Interpretation: MLSA-LAM and MLCwA at both high (1.0 mg) and low (0.1 mg) doses were found to be safe for use in humans without known exposure to leprosy and in target populations. At a sensitivity rate of 20–25% these antigens are not suitable as a skin test for the detection of the early stages of leprosy infection; however, the degree of specificity is impressive given the presence of cross-reactive antigens in these complex native M. leprae preparations. Trial Registration: ClinicalTrails.gov NCT01920750 (Phase I), NCT00128193 (Phase II)

/pdf/safety-and-efficacy-assessment-of-two-new-leprosy-skin-test-58879yq6ya.pdf

Safety and efficacy assessment of two new leprosy skin test antigens: randomized double blind clinical study.

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Safety and efficacy assessment of two new leprosy skin test antigens: randomized double blind clinical study.