Serological responses to prednisolone treatment in leprosy reactions: study of TNF-α, antibodies to phenolic glycolipid-1, lipoarabinomanan, ceramide and S100-B.

BACKGROUND: Corticosteroids have been extensively used in the treatment of immunological reactions and neuritis in leprosy. The present study evaluates the serological response to steroid treatment in leprosy reactions and neuritis. METHODS: Seven serological markers [TNF-α, antibodies to Phenolic glycolipid-1 (PGL-1 IgM and IgG), Lipoarabinomannan (LAM IgG1 and IgG3), C2-Ceramide and S100 B] were analyzed longitudinally in 72 leprosy patients before, during and after the reaction. At the onset of reaction these patients received a standard course of prednisolone. The levels of the above markers were measured by Enzyme linked immunosorbent assay (ELISA) and compared with the individuals own value in the month prior to the reaction and presented as percentage increase. RESULTS: One month before the reaction individuals showed a varying increase in the level of different markers such as TNF-α (53%) and antibodies to Ceramide (53%), followed by to PGL-1 (51%), S100B (50%) and LAM (26%). The increase was significantly associated with clinical finding of nerve pain, tenderness and new nerve function impairment. After one month prednisolone therapy, there was a fall in the levels [TNF-α (60%), C2-Ceramide (54%), S100B (67%), PGL-1(47%) and LAM (52%)] with each marker responding differently to steroid. CONCLUSION: Reactions in leprosy are inflammatory processes wherein a rise in set of serological markers can be detected a month before the clinical onset of reaction, some of which remain elevated during their action and steroid treatment induces a variable fall in the levels, and this forms the basis for a variable individual response to steroid therapy

Analysis of Antibody and Cytokine Markers for Leprosy Nerve Damage and Reactions in the INFIR Cohort in India

Leprosy is one of the oldest known diseases. In spite of the established fact that it is least infectious and a completely curable disease, the social stigma associated with it still lingers in many countries and remains a major obstacle to self reporting and early treatment. The nerve damage that occurs in leprosy is the most serious aspect of this disease as nerve damage leads to progressive impairment and disability. It is important to identify markers of nerve damage so that preventive measures can be taken. This prospective cohort study was designed to look at the potential association of some serological markers with reactions and nerve function impairment. Three hundred and three newly diagnosed patients from north India were recruited for this study. The study attempts to reflect a model of nerve damage initiated by mycobacterial antigens and maintained by ongoing inflammation through cytokines such as Tumour Necrosis Factor alpha and perhaps extended by antibodies against nerve components

Predicting neuropathy and reactions in leprosy at diagnosis and before incident events. Results from the INFIR cohort study

BackgroundLeprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions.Methodology/Principal FindingsThe study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event.Conclusions/SignificanceThese findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability

Detection of viable Mycobacterium leprae in soil samples: insights into possible sources of transmission of leprosy

Leprosy has ceased to be a public health problem world wide, after the successful implementation of effective chemotherapy (MDT) and use of control measures. However, new cases of leprosy continue to occur. Mycobacterium leprae cannot be grown in any acceptable culture medium and besides the wild armadillos, there is no known animal reservoir for leprosy. The transmission of leprosy is believed to be due to a large extent by droplet discharge of bacilli through nose and mouth and to a lesser extent by direct contact of susceptible host with a patient for long duration. The exact role of the environment in the transmission dynamics is still speculative. In the present study, we have tried to detect viable M. leprae from soil samples in endemic areas by using molecular methods. Eighty soil samples were collected from villages of this area, DNA and RNA of M. leprae extracted and identified using specific M. leprae primers. PCR amplification was done and real-time RT-PCR was used to detect viable M. leprae. DNA targeting the 16S region of M. leprae was detected in 37.5%, whereas M. leprae RNA targeting the same region was detected in 35% of these samples. Of the total 80 samples, 40 were collected from residential areas of leprosy patients whereas 40 samples were from no-patient areas. Fifty-five percent positivity for 16S rRNA of M. leprae was observed from the "patient"area in comparison to 15% positivity from the "no-patient"area (p < 0.001). This study thus provides valuable information of presence of viable M. leprae in soil specimens, which would be of use in investigating the transmission dynamics in leprosy