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

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.

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.

A comparison of the change in clinical severity scale score and a retrospective physician assessment of neurological outcome in individuals with leprosy associated nerve function impairment after treatment with corticosteroids.

Objectives: To determine whether the measured change in score of a validated clinical severity scale reflected physician assessed improvement in individuals who had received corticosteroid therapy for leprosy associated nerve damage.

Design: Patients with nerve function impairment who participated in a randomised controlled trial of corticosteroids were classified into two groups using a retrospectively determined physician assessment of improvement. One group consisted of patients who had recovered or improved the other of patients who were unchanged or had deteriorated.

A phase two randomised controlled double blind trial of high dose intravenous methylprednisolone and oral prednisolone versus intravenous normal saline and oral prednisolone in individuals with leprosy type 1 reactions and/or nerve function impairment.

Background: Leprosy Type 1 reactions are a major cause of nerve damage and the preventable disability that results. Type 1 reactions are treated with oral corticosteroids and there are few data to support the optimal dose and duration of treatment. Type 1 reactions have a Th1 immune profile: cells in cutaneous and neural lesions expressing interferon-γ and interleukin-12.

Association of TNF, MBL, and VDR polymorphisms with leprosy phenotypes.

Although genetic variants in tumor necrosis factor (TNF), mannose binding lectin (MBL), and the vitamin D receptor (VDR) have been associated with leprosy clinical outcomes, these findings have not been extensively validated. We used a case-control study design with 933 patients in Nepal, which included 240 patients with type I reversal reaction (RR), and 124 patients with erythema nodosum leprosum (ENL) reactions. We compared genotype frequencies in 933 cases and 101 controls of seven polymorphisms, including a promoter region variant in TNF (G -308A), three polymorphisms in MBL (C154T, G161A and G170A), and three variants in VDR (FokI, BsmI, and TaqI).

Common polymorphisms in the NOD2 gene region are associated with leprosy and its reactive states.

Background: Because of its wide spectrum of clinical manifestations and its well-defined immunological complications, leprosy is a useful disease for studying genetic regulation of the host response to infection. We hypothesized that polymorphisms in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene, for a cytosolic receptor known to detect mycobacteria, are associated with susceptibility to leprosy and its clinical outcomes.

Methods: We used a case-control study design with 933 patients in Nepal.

Comparative genomic and phylogeographic analysis of Mycobacterium leprae.

Reductive evolution and massive pseudogene formation have shaped the 3.31-Mb genome of Mycobacterium leprae, an unculturable obligate pathogen that causes leprosy in humans. The complete genome sequence of M.

From genome-based in silico predictions to ex vivo verification of leprosy diagnosis.

The detection of hundreds of thousands of new cases of leprosy every year suggests that transmission of Mycobacterium leprae infection still continues. Unfortunately, tools for identification of asymptomatic disease and/or early-stage M. leprae infection (likely sources of transmission) are lacking.

Selection of antigens and development of prototype tests for point-of-care leprosy diagnosis.

Leprosy can be a devastating chronic infection that causes nerve function impairment and associated disfigurement. Despite the recent reduction in the number of registered worldwide leprosy cases as a result of the widespread use of multidrug therapy, the number of new cases detected each year remains relatively stable. The diagnosis of leprosy is currently based on the appearance of clinical signs and requires expert clinical, as well as labor-intensive and time-consuming laboratory or histological, evaluation.

Human TLR1 deficiency is associated with impaired mycobacterial signaling and protection from leprosy reversal reaction.

Toll-like receptors (TLRs) are important regulators of the innate immune response to pathogens, including Mycobacterium leprae, which is recognized by TLR1/2 heterodimers. We previously identified a transmembrane domain polymorphism, TLR1_T1805G, that encodes an isoleucine to serine substitution and is associated with impaired signaling. We hypothesized that this TLR1 SNP regulates the innate immune response and susceptibility to leprosy.

Development and evaluation of a novel multiple-primer PCR amplification refractory mutation system for the rapid detection of mutations conferring rifampicin resistance in codon 425 of the rpoB gene of Mycobacterium leprae.

Rifampicin-resistant Mycobacterium leprae is regularly reported and drug resistance is a major threat for the elimination of leprosy. There is an urgent need for a simple method that can detect rifampicin resistance in clinical isolates. This study developed a multiple-primer PCR amplification refractory mutation system, a simple, reliable and economical method for clinical specimens that allowed the rapid detection of mutations in the nucleotides of the codon for Ser425 of the M.

Rapid differentiation of Mycobacterium tuberculosis and Mycobacterium leprae from sputum by polymerase chain reaction.

Differentiation of M tuberculosis and M leprae by polymerase chain reaction (PCR), when acid-fast bacilli (AFB) were present in sputum from patients at Anandaban hospital, was carried out. Thirty sputum samples microscopy positive for AFB were collected and were subjected to culture. Bacterial DNA was extracted and PCR was performed using primers specific for Mycobacterium tuberculosis and Mycobacterium leprae DNA.

Off-site manufacturing significantly beneficial.

Off-site manufacture of energy centre systems could help the NHS improve its track record of delivering major projects on time and on budget, argues Murdo MacDonald, major projects manager for Spirax Sarco.

Reverse line probe assay for the rapid detection of rifampicin resistance in Mycobacterium leprae.

Mutations in the rpoB gene of 40 biopsy isolates of Mycobacterium leprae were analyzed by reverse hybridization-based line probe assay after PCR, and nine distinct single-nucleotide substitutions were found. Among them, a 3-nucleotide substitution was found in two, and 2-nucleotide substitutions were found in seven isolates. This is a new finding of multiple mutations in a single point of the rpoB gene for rifampicin resistance.

Effective treatment of erythema nodosum leprosum with thalidomide is associated with immune stimulation.

The immunomodulatory drug thalidomide is the treatment of choice for erythema nodosum leprosum (ENL), an inflammatory cutaneous and systemic complication of multibacillary leprosy. To elucidate the mechanism of action of thalidomide in this syndrome, we prospectively investigated 20 patients with ENL who were treated with thalidomide for 21 days. All patients responded to treatment, with the majority of them having complete resolution of cutaneous lesions within 7 days.

An approach to understanding the transmission of Mycobacterium leprae using molecular and immunological methods: results from the MILEP2 study.

Background: The current strategy for leprosy control using case detection and treatment has greatly reduced the prevalence of leprosy, but has had no demonstrable effect on interrupting transmission.

Methods: Three leprosy endemic communities in India were recruited, examined, and followed up sequentially over 2 yrs using nasal swabs and saliva collections. The nasal swabs were tested by polymerase chain reaction for the presence of M.