Elimination of leprosy &amp; possibility of eradication – the Indian scenario

Kv, Desikan

doi:10.4103/0971-5916.93415

Cited by 23 publications

(17 citation statements)

References 2 publications

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“…[12] Pockets of high endemicity still remain in some areas of India[1] like Bihar and Chattisgarh which are yet to achieve elimination (with a prevalence rate of 1.12 and 1.94, respectively). [3]…”

Section: Global and Indian Scenariomentioning

confidence: 99%

Fixed-duration therapy in leprosy: Limitations and opportunities

Munisamy

Thappa

2013

Indian J Dermatol

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Leprosy has been considered a curable disease after the implementation of multidrug therapy (MDT), which has been proven to be safe and effective, by bringing about a significant change in the global and national scenario of leprosy by upgrading the control of leprosy to the next stage of eradication. Since its introduction, the MDT regimens for the treatment of leprosy have undergone several changes especially with regard to the duration of treatment. The advantages of shortened duration of treatment need to be balanced against the risk of relapse and a lot of controversies exist pertaining to this aspect. The fixed-duration (FD) therapy is not popular among academicians and private practitioners who prefer precise diagnosis and treatment with superior MDT regimens and for a longer duration. On the contrary, from a public health-care point of view, precise diagnosis and a longer treatment schedule are not cost effective and not feasible to be implemented in elimination programs. Hence, a fine balance needs to be maintained between achieving a cure for the patient and protecting the society at risk, and this review discusses the various limitations and opportunities of FD therapy with a note on the newer MDT regimens.

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Section: Global and Indian Scenariomentioning

confidence: 99%

Fixed-duration therapy in leprosy: Limitations and opportunities

Munisamy

Thappa

2013

Indian J Dermatol

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“…In India, the prevalence rate for leprosy before the initiation of MDT was 24/10,000 population. With the introduction of MDT, this figure was reduced to less than 1/10,000 population in the year 2005 [Desikan, ]. There is inadequate understanding on the modes of entry, gene regulation, metabolism, and survival of M. leprae in the host.…”

mentioning

confidence: 99%

Computational Modelling of Dapsone Interaction With Dihydropteroate Synthase in Mycobacterium leprae; Insights Into Molecular Basis of Dapsone Resistance in Leprosy

Chaitanya

Das

Bhat

et al. 2015

J of Cellular Biochemistry

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The molecular basis for determination of resistance to anti-leprosy drugs is the presence of point mutations within the genes of Mycobacterium leprae (M. leprae) that encode active drug targets. The downstream structural and functional implications of these point mutations on drug targets were scarcely studied. In this study, we utilized computational tools to develop native and mutant protein models for 5 point mutations at codon positions 53 and 55 in 6-hydroxymethyl-7, 8-dihydropteroate synthase (DHPS) of M. leprae, an active target for dapsone encoded by folp1 gene, that confer resistance to dapsone. Molecular docking was performed to identify variations in dapsone interaction with mutant DHPS in terms of hydrogen bonding, hydrophobic interactions, and energy changes. Schrodinger Suite 2014-3 was used to build homology models and in performing molecular docking. An increase in volume of the binding cavities of mutant structures was noted when compared to native form indicating a weakening in interaction (60.7 Å(3) in native vs. 233.6 Å(3) in Thr53Ala, 659.9 Å(3) in Thr53Ile, 400 Å(3) for Thr53Val, 385 Å(3) for Pro55Arg, and 210 Å(3) for Pro55Leu). This was also reflected by changes in hydrogen bonds and decrease in hydrophobic interactions in the mutant models. The total binding energy (ΔG) decreased significantly in mutant forms when compared to the native form (-51.92 Kcal/mol for native vs. -35.64, -35.24, -46.47, -47.69, and -41.36 Kcal/mol for mutations Thr53Ala, Thr53Ile, Thr53Val, Pro55Arg, and Pro55Leu, respectively. In brief, this analysis provided structural and mechanistic insights to the degree of dapsone resistance contributed by each of these DHPS mutants in leprosy.

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“…Some important questions must be answered concerning effectiveness of interventions to reduce transmission and the source of infection and strategies under the national leprosy elimination programme (NLEP). [10,11] National leprosy programs now encourage people to come forward for treatment by information, education, communication (IEC) activities, and recommend limiting leprosy services to general health facilities. [8] Low levels of awareness, high social stigma, ignorance of a painless patch, long incubation period and late neurological manifestations are hindrances to the patient seeking health care in the early stages.…”

Section: Discussion Discussionmentioning

confidence: 99%