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Background: Clinical data on pure-neuritic leprosy (PNL) is limited., Objective: To study the clinical and epidemiological features of PNL in the leprosy post-elimination era., Methods: This was a retrospective analysis of the clinic records of leprosy patients from January 2006 to June 2013. Data regarding age, sex, disease duration, presenting complaints, nerves affected, complications and treatment received were extracted from PNL cases., Results: Among 906 registered leprosy cases, 48 (5·3%) were found to have PNL. The mean age was 36·9 ± 16·2 years and predominantly males were affected (85·4%). The mean delay between onset of symptoms and diagnosis was 2·1 ± 2·2 years. Multiple nerves were affected in 36 patients (75%) and 12 (25%) had only one nerve involved. Visible deformities at presentation were noted in 32 (66·7%) patients. Forty patients (83·3%) were treated with multi drug therapy-multibacillary (MDTMB) regimen and three (6·25%) were treated with MDT-paucibacillary regimen. Twenty-one patients (43·8%) were considered positive responders to treatment. There was no correlation between the duration of NFI and treatment outcome., Conclusion: PNL continues to occur in the post-elimination era. Grade 2 deformities are common in PNL compared to other leprosy patients because of delayed diagnosis and treatment. Distinct diagnosis and treatment guidelines and sensitisation of health care workers and physicians to the occurrence of PNL is the need of the day.

Background: Mycobacterium leprae and HIV cause infectious diseases of great concern for the public health care sector worldwide. Both are especially worrisome diseases when patients become co-infected and exhibit the expected clinical exuberance. The objective of this study was to evaluate episodes of reversal reaction (RR) and the effect of the use of corticosteroids on the treatment of borderline tuberculoid leprosy patients co-infected with the human immunodeficiency virus (HIV)., Methods: This is a retrospective cohort study in which the clinical manifestations of the patients and their responses to corticosteroid therapy were observed. Variables were analysed during and after multidrug therapy between the first and last days of prednisone, which occurred up to a maximum of 6 months after initiating corticosteroid therapy., Results: A total of 22 HIV-positive and 28 HIV-negative cases were included. Loss of sensitivity and neural thickening were statistically significant while clinically ulcerated lesions were only observed in the co-infected group. Most patients were diagnosed with leprosy in the presence of RR and six patients manifested RR as an immune reconstitution inflammatory syndrome. On average, both groups received similar doses of corticosteroids (difference of 0·1 mg/kg/day).

Unlabelled: The working hypothesis is that, viable Mycobacterium leprae (M. leprae) play a crucial role in the precipitation of Type 1 reaction (T1R) in leprosy., Material and Methods: A total of 165 new multibacillary patients were studied. To demonstrate presence of viable M. leprae in reactional lesion (T1R+), three tests were used concurrently viz. growth in the mouse foot pad (MFP), immunohistochemical detection of M. leprae secretory protein Ag85, and 16s rRNA--using in situ RT-PCR. Mirror biopsies and non reactional lesions served as controls (T1R-)., Findings: A significantly higher proportion of lesion biopsy homogenates obtained at onset, from T1R(+) cases have shown unequivocal growth in MFP, proving the presence of viable bacteria, as compared to T1R(-) (P < 0.005). In contrast, few Mirror biopsies were positive in both T1R(+) and T1R(-). With respect to Ag85, while the overall positivity was higher in T1R(+) (74%), however the intensity of staining (Grade 2+) was disproportionately higher in T1R(+) BT-BB lesions 11/20 (55%). In the rebiopsies obtained during a repeat episode of T1R, Ag 85 as well as 16s rRNA, positivity (62% & 100%) was higher in T1R(+). It is inferred therefore 'viable' bacteria are an essential component in T1R and difference in the quality of bacilli, not the quantity or the ratio of dead to viable play a role in the precipitation of T1R. In conclusion, the findings show that 'metabolically active' M. leprae is a component/prerequisite and the secretory protein Ag 85, might be the trigger for precipitation of T1R.

Background: Though the World Health Organization declared the 'elimination of leprosy as public health problem' in 2000, the disease remains endemic in many countries. Current trends in incidence of infection and disease are unclear., Methods: Data on leprosy prevalence between 1977-2013 and data on new leprosy cases detected in the Republic of Korea between 1989-2013 were analysed by age, sex, clinical types, mode of detection, family history, disability grading and geographical distribution., Results: Both prevalence and incidence have declined greatly. There has been a shift to an increased proportion of multibacillary disease, and older age groups, consistent with a dramatic decrease in infection transmission in recent decades. An increase in proportion of cases with family history of disease is consistent with these declines. There is evidence that declines in infection and disease have been greater in the north of the country, as revealed in patterns by place of birth over time. Cases in immigrants now form a substantial proportion of leprosy disease in the Republic of Korea., Conclusions: Leprosy has declined dramatically in the Republic of Korea in recent decades, and transmission of M. leprae may have effectively stopped. There remains a burden of care for individuals whose disease developed in the past, and there may be some additional newly detected cases among immigrants and among older individuals who acquired autochthonous infections decades ago.

Leprosy, one of the oldest diseases known to man, is a stigmatising, potentially disabling disease. Throughout history, leprosy has been associated with fear, prejudice and immense social stigma. It remains one of the leading causes of deformity and physical disability from an infectious disease. Tremendous advances in leprosy control were made by the World Health Organization, and the 'elimination of leprosy', defined as a decrease of disease prevalence to less than 1 case per 10,000 population, was achieved by 2000. However, the reality is that true 'elimination' is yet to be achieved. Despite almost 30 years of effective multidrug treatment, the prevalence and incidence of leprosy have plateaued since 2005. Moreover, new cases with Grade 2 disability and new cases occurring in children remain unchanged since 2010, reflecting a failure in early leprosy detection, and indicating that transmission is clearly continuing. This review examines the challenges of elimination, and proposes further measures to reduce the disease burden, including future research possibilities.

Unlabelled: Summary, Background: The transmission pathways of Mycobacterium leprae are not fully understood. Solid evidence exists for an increased risk for individuals living in close contact with leprosy patients but the existence of zoonotic leprosy, environmental reservoirs and trauma-related transmission has also been established., Purpose: To assess the current state of knowledge on M. leprae transmission, we conducted a systematic review of the peer-reviewed literature pertaining to this topic., Method: Major electronic bibliographic databases were searched for relevant peer-reviewed articles published up to January 2014. No restrictions on study types, participants and location were applied, and all outcomes demonstrated to contribute to the transmission of M. leprae were considered. Included studies were grouped by mode of transmission, namely (i) human-to-human via aerosols or direct contact; (ii) direct inoculation (e.g. injury); and (iii) transmission to humans from environmental or zoonotic reservoirs, and by insects. The importance of the different transmission pathways and the strength of the evidence were assessed considering the number of publications describing similar findings, the consistency of the findings and the methodological quality of the studies., Results: A total of 79 relevant articles were retained out of 3,805 hits resulting from the application of the search strategy. Solid evidence for transmission among contacts exists, and for zoonotic leprosy in the southern States of the USA. Based on the extant evidence, skin-to-skin contact, aerosols/droplets and shedding of bacteria into the environment and subsequent infection, e.g. through dust or small wounds, all remain possible options., Conclusion: No study has unequivocally demonstrated the mechanisms by which M. leprae bacteria travel from one case of leprosy to another.

The need for rapid diagnostic tests that can be applied in non-expert settings may now be greater than ever before, due to changes in leprosy control programmes and the decrease in special expertise required for (early) diagnosis of leprosy. However, there is no test available that can detect asymptomatic Mycobacterium leprae infection or predict progression of infection to clinical disease. The characteristics of the leprosy disease spectrum, in which both cellular and humoral immunity against M. leprae determine the outcome of infection, are pre-eminently suitable for development of tests that simultaneously detect biomarkers specific for both types of immune responses, thereby covering the complete immunological leprosy spectrum. Since publication of the M. leprae genome, many research groups have investigated the potential of M. leprae-unique antigens in serologic as well as T cell assays. Despite the early promise of the genome towards identifying antigens that induce M. leprae-specific T cells, it took more than a decade before promising candidates were identified. This review describes recent studies on M. leprae-specific T cell responses and discusses the application of measuring specific cellular mediated immune responses possibly combined with serologic responses in field-friendly tests for early diagnosis of M. leprae exposure and infection.

PGL-I (phenolic glycolipid I) emerged in the early 1980s on the one hand as part of intensive efforts to define the typing antigens of a host of Mycobacterium spp. and also from characterisation of the lipids of skin biopsies from highly bacillary positive lepromatous leprosy patients. PGL-I, despite its extreme lipophilicity due to its inherent phthiocerol dimycocerosyl component, is highly antigenic evoking high titre IgM antibodies in lepromatous leprosy patients, attributable largely to the unique 3,6-di-O-methyl-beta-D-glucosyl entity at the non-reducing terminus of its trisaccharide. PGL-I itself or in the form of semisynthetic neoglycoproteins containing the synthetic terminal disaccharide or the whole trisaccharide chemically conjugated to such as bovine or human serum albumin, has found its greatest utility in the serological diagnosis, confirmation and management of lepromatous leprosy. PGL-I has also been implicated in the tropism of M. leprae for Schwann cells, through specific binding to laminin, and to play an important role in downregulation of the inflammatory immune response and inhibition of dendritic cell maturation and activation, thereby facilitating the persistence of M. leprae/leprosy.

Objective: The immune-mediated events that precipitate erythema nodosum leprosum (ENL) are not well understood. One component may be the complexing of antibody with antigens released from infected macrophages, the activation of complement and the subsequent local inflammation. We assess here the ability of highly-purified, disrupted M. leprae, to activate complement., Results: Intact and sonically-disrupted crude and alkali-purified nu/nu mouse-derived M. leprae suspensions were incubated with normal serum and a hemolytic titer (CH50) was determined as a measure of complement fixation. Crude M. leprae consumed complement, and disrupted preparations more than the intact. Purified M. leprae preparations did not consume complement unless disrupted., Conclusion: M. leprae, if disrupted, can activate complement. This supports a hypothesis that links released antigens with ENL, and may explain the increased probability of an occurrence of ENL following chemotherapy.

Introduction: The ML Flow test is an immunochromatographic assay that detects IgM antibodies against M. leprae-specific anti-phenolic glycolipid I (PGL-I). In addition to slit skin smears stained by the Ziehl-Neelsen technique, it can be helpful in the operational classification of leprosy patients for treatment purposes., Objective: This work studied the relationship between antibody levels as detected by semi-quantitative ML Flow serologic test and bacterial load as quantified by slit skin smear., Patients and Methods: 135 patients with newly detected leprosy at the reference service in Sanitary Dermatology in Brazil had slit skin smears (registered as bacillary index - BI) and an ML Flow test (registered qualitatively and semi-quantitatively) performed at admission. A logistic regression and agreement measures (kappa index) were calculated., Results: Slit skin smears were positive in 35.9% of patients and 57% of patients were seropositive for PGL-1 antibodies. Among the seropositive patients, 416% had five or fewer skin lesions, and 65.8% had more than one peripheral nerve involved. Slit skin smears were positive in only three seronegative patients (5.6%), and negative in 41.9% of seropositive patients. Patients with a BI of 4 + had an OR of 33 for being seropositive in comparison to those with a low BI., Conclusions: There is a correlation between serologic test and slit skin smear results. Therefore, an ML Flow test may become a useful tool in the clinical classification of leprosy, besides slit skin smears, which require a proper laboratory infrastructure and experienced personnel.

Objective: To investigate using the mouse footpad system, whether the use of cryopreservants help in retaining the viability of Mycobacterium leprae samples stored at three different temperatures of 4 degrees, -20 degrees and -70 degrees C for 30 days., Design: Biopsies from eight untreated lepromatous leprosy cases were homogenised and inoculated into footpads of normal Swiss White mice within 24 hours (control) and remaining homogenates in each case was divided and stored at 4 degrees C, -20 degrees C and -70 degrees C respectively for 1 month, using either 10% skimmed milk (SM) or Roswell Park Memorial Institute media + 10% glycerol (RPMI) (test). Homogenates adjusted to contain 1 x 10(4) M. leprae/footpad was inoculated into 10 mice per set. Harvestings were done at 6th, 7th, 8th and 12th months. Footpad counts showing > 1 x 10(5) M. leprae at 6th month or later were considered as positive yield., Results: Control All the cases showed > 100 fold growth and 100% take. Viability at 4 degrees C: Only one case (SM) showed a 100 fold increase and 23% take. Viability at -20 degrees C: Two cases showed fold growth that was 40-60 fold less with takes of 63% (SM) and 71% (RPMI) respectively. Viability at -70 degrees C: Positivity was 45% but the fold increase was less as compared to control and takes were between 80-20%, except one RPMI where take was 100%., Conclusion: The viability assessed using the mouse footpad was best and consistent in the inoculas that were injected within 24 hours of harvest from the host tissue (control group). None of the storage temperatures used matched with the controls with respect to bacterial yield or % takes. Among the three storage temperatures, -70 degrees C appeared to be better with 45% of the samples showing growth. There was no significant difference noted between the two preservatives used.

Although multiplication of Mycobacterium leprae in the foot pads of immune-competent mice is limited, and no leprosy-like lesions are produced in these animals, the mouse foot-pad system represents the first truly useful and reproducible animal model of M. leprae infection. Its employment has enabled research into basic questions with respect to the microbiology of M. leprae, and the epidemiology, treatment and control of leprosy. The mouse foot-pad technique is labour-intensive and time-consuming, and is expensive in terms of the costs of animal purchase and maintenance. In addition, the technique appears to be rather imprecise and insensitive, compared with the techniques employed in working with cultivable micro-organisms. For these reasons, and also as a by-product of the success of multi-drug therapy, the technique has been abandoned in many research centres. Nevertheless, until a more simple and sensitive technique for demonstrating the viability of M. leprae is developed, the mouse foot-pad system remains an essential tool for leprosy research. In this review, we discuss the mouse foot-pad technique in detail, analyse its precision, point out its shortcomings, describe its most important applications, and prescribe a method by which to assess the ability of an alternative technique to serve in place of this established technique.

The obligate intracellularism of Mycobacterium leprae may be attributable to the effects of mutations in major metabolic areas due to a genome capable of encoding only about 1600 proteins. Yet cell wall biosynthesis capability remains relatively intact and comparisons with the genome of Mycobacterium tuberculosis provide insights into the genetic basis of a minimal mycobacterial cell wall.

In connection with a 56-day controlled clinical trial for comparing the therapeutic effects between pefloxacin and ofloxacin in 21 lepromatous patients, we have studied the relationships between PGL-1 antigen level in serum and in skin and serum PGL-1 antibody titre on the one hand, and the viability of Mycobacterium leprae, as measured by serial mouse footpad inoculations, and other bactericidal parameters on the other. Before and during treatment, significant correlation was found between serum PGL-1 level and the morphological index (MI), and with the number of viable organisms per mg skin tissue. However, neither serum PGL-1 antibody titre nor skin PGL-1 antigen level showed significant change during the 56-day trial. Because the reduction of serum PGL-1 level was well correlated but less pronounced as compared with the evolution of viable organisms during treatment, the serum PGL-1 antigen assay may be useful as an early indicator of response to chemotherapy in short-term clinical trial, but it is unlikely to replace mouse footpad inoculation for the evaluation of viability of M. leprae.