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.
BackgroundThe ILEP Nerve Function Impairment in Reaction (INFIR) is a cohort study designed to identify predictors of reactions and nerve function impairment (NFI) in leprosy.Aim of the StudyAntibodies to mycobacteria, nerve components and serum cytokine were measured as potential markers for their possible association with reactions and NFI.Patients and Methods303 newly diagnosed leprosy patients from two centres in North India were enrolled. Antibodies to PGL-1, LAM (IgG1 and IgG3), ceramide, S100 and TNFα levels were measured using ELISA techniques.ResultsS-100, PGL IgG and IgM antibody levels were lowest in patients with BT leprosy and highest in patients with lepromatous leprosy. LAM IgG1 and LAM IgG3 antibody levels were highest in patients with BL leprosy. Ceramide antibody levels were not correlated with type of leprosy. Levels of all the antibodies tested and TNF α were lowest in patients with only skin reaction. PGL IgM antibody levels were elevated in patients with skin reactions and NFI. Old sensory NFI is associated with significant elevation of PGL IgG, LAM IgG and S100 antibody levels.ConclusionThese results reveal that the antibody response to mycobacterial antigens, nerve antigens and cytokines are in a dynamic flux and could collectively contribute to NFI in leprosy. The association of multiple markers with old NFI may indicate the contribution of different pathological processes.
Leprosy continues to be a significant health problem in certain pockets in developing countries. Better understanding of the transmission and source of the infection would help to decipher the transmission link, leading to control of the spread of the disease. The nose is considered to be a portal of entry, suggesting an aerial route for transmission through droplet infection. The evidence suggests that many individuals from endemic countries carry Mycobacterium leprae in their nasal cavities without having obvious symptoms of leprosy. The objective of the present study was to assess the presence of M. leprae on the nasal mucosa in the general population from a leprosy-endemic pocket. M. leprae detection was carried out using PCR targeting RLEP. Four hundred subjects from an area highly endemic for leprosy were included in the study and followed up during three different seasons--winter, summer, and monsoon--for evidence of nasal exposure to M. leprae. PCR positivity for M. leprae was observed in 29%, 21% and 31% of the samples collected in winter, summer and the monsoon season, respectively. Twenty-six individuals from the cohort showed amplification for M. leprae for all seasons. Our results are consistent with reports in the literature showing widespread exposure to M. leprae in the endemic community. The results also suggest possible association of the environmental conditions (climate) with the transmission pattern and levels of exposure to M. leprae. However, the present study indicated that the population from highly endemic pockets will have exposure to M. leprae irrespective of season.
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