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• W2061738367 abstract "Dear Sirs, We read with interest the article by Linder et al. on “Relapses versus reactions in multibacillary leprosy: proposal of new relapse criteria”, published in the March 2008 issue of Tropical Medicine and International Health (Linder et al. 2008). The authors describe an important issue in leprosy case management, namely the distinction between reactions and relapses in leprosy patients who received previous treatment. As these require radically different treatment, it is indeed important to make this distinction and a set of criteria, in combination with expert clinical assessment, may contribute to this. The authors also rightly state that “A reliable determination of relapse rate is the single most important parameter to determine the efficacy of multi-drug therapy (MDT)”. This has important implications for control activities, as declining or even low efficacy of MDT may point towards (increasing) drug resistance. It is therefore mandatory not only to make the distinction between relapse and reaction, but also between relapse and re-infection. Unfortunately, the authors do not explore this issue in their article. None of the main criteria used by the authors - time since treatment, a higher-than-expected BI or validation by the presence of live bacteria as witnessed from the mouse footpad assay - can make the distinction between relapse and re-infection. Tuberculosis is caused by Mycobacterium tuberculosis, an organism closely related to Mycobacterium leprae, and in both tuberculosis (TB) and leprosy genetic parameters and immunological processes play a role in determining the outcome of infection: some individuals are more susceptible than others. Moreover, there is no evidence for either TB or leprosy that successful treatment protects against future disease. It is known from studies on TB that in areas with high TB incidence and/or high HIV positivity rates, recurrence rates are high and exogenous re-infection occurs regularly (Sonnenberg et al. 2001). However, leprosy has a relatively low incidence and prevalence: Lindner et al. describe an incidence of 0.21/10,000 for Karachi in 2004. Although it is well documented that even in areas with a strong leprosy control program where there are many more undetected patients around (Moet et al. 2008), the chances of re-infection seem to be relatively low. However, it is known from studies on TB in low-endemic areas that re-infections occur regularly: in northern Italy 5 of the 32 patients who had two episodes of TB had different fingerprints indicating exogenous infection (Bandera et al. 2001); in Spain 5 of 13 cases had different MIRU-VNTR typing patterns (Martin et al. 2007). The TB studies make use of molecular strain typing methods. Unfortunately, these were until recently not available for leprosy, making it impossible to distinguish between relapse and re-infection. However, recent years have seen the development of a number of molecular targets that now also allow strain differentiation for leprosy. Monot and co-workers very elegantly showed the presence of different SNP alleles in M.leprae strains from different parts of the world and were thus able to follow the spread of the leprosy bacterium across the globe (Monot et al. 2005). At a more local level, VNTRs can help to distinguish between different strains and may help to assess transmission patterns as well as determine whether a second episode of leprosy is due to relapse or reinfection. A number of articles have described the use of VNTRs (among others: Matsuoka et al. 2000; Zhang et al. 2005; Weng et al. 2007;Young et al. 2008). The Initiative for Diagnostic and Epidemiological Assays for Leprosy (IDEAL), a consortium of 30 laboratory and field research groups from around the world in which most of the groups that have described VNTR-studies so far collaborate, is currently developing a standard set of well-evaluated VNTRs. We expect that molecular strain typing using VNTRs will be able to answer questions regarding transmission, relapse and reinfection. We therefore would strongly suggest that any groups or control programs interested in assessing relapse rates collect and store slit skin smear and/or biopsy samples from their patient population. The original infecting strain can then be compared with the new strain. In this way it will in future be possible to not only make the distinction between relapse and reaction, as proposed by Linder et al., but also truly answer the question whether a patient is suffering from a relapse or has a second episode of leprosy due to re-infection." @default.
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• W2061738367 date "2008-10-01" @default.
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• W2061738367 title "Molecular methods for distinguishing between relapse and reinfection in leprosy" @default.
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• W2061738367 doi "https://doi.org/10.1111/j.1365-3156.2008.02134_1.x" @default.
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