Implications of drug resistance in leprosy: disease course, reactions and the use of novel drugs.

Leprosy remains a significant neglected tropical disease despite the goal of elimination having been achieved in various endemic nations over the past two decades. Reactional episodes complicate the disease course, resulting in deformities and disability. The main aim of treatment is to kill Mycobacterium leprae and decrease the bacterial load, which could help prevent further bacilli transmission.

Treatment and Evaluation Advances in Leprosy Neuropathy.

Neuropathy and related disabilities are the major medical consequences of leprosy, which remains a global medical concern. Despite major advances in understanding the mechanisms of M. leprae entry into peripheral nerves, most aspects of the pathogenesis of leprosy neuropathy remain poorly understood.

Isolation of Mycobacterium lepromatosis and Development of Molecular Diagnostic Assays to Distinguish Mycobacterium leprae and M. lepromatosis.

Background: Mycobacterium leprae was thought to be the exclusive causative agent of leprosy until Mycobacterium lepromatosis was identified in a rare form of leprosy known as diffuse lepromatous leprosy (DLL).

Methods: We isolated M. lepromatosis from a patient with DLL and propagated it in athymic nude mouse footpads.

An enhanced regimen as post-exposure chemoprophylaxis for leprosy: PEP+.

The ongoing transmission of Mycobacterium (M.) leprae reflected in a very slow decline in leprosy incidence, forces us to be innovative and conduct cutting-edge research. Single dose rifampicin (SDR) as post-exposure prophylaxis (PEP) for contacts of leprosy patients, reduces their risk to develop leprosy by 60%.

qPCR-High resolution melt analysis for drug susceptibility testing of Mycobacterium leprae directly from clinical specimens of leprosy patients.

Background: Real-Time PCR-High Resolution Melting (qPCR-HRM) analysis has been recently described for rapid drug susceptibility testing (DST) of Mycobacterium leprae. The purpose of the current study was to further evaluate the validity, reliability, and accuracy of this assay for M. leprae DST in clinical specimens.

Zoonotic Leprosy in the Southeastern United States.

Nine-banded armadillos (Dasypus novemcinctus) are naturally infected with Mycobacterium leprae and have been implicated in zoonotic transmission of leprosy. Early studies found this disease mainly in Texas and Louisiana, but armadillos in the southeastern United States appeared to be free of infection. We screened 645 armadillos from 8 locations in the southeastern United States not known to harbor enzootic leprosy for M.

Tuberculosis and Leprosy: Classical Granulomatous Diseases in the Twenty-First Century.

Leprosy and tuberculosis are chronic mycobacterial infections that elicit granulomatous inflammation. Both infections are curable, but granulomatous injury to cutaneous structures, including cutaneous nerves in leprosy, may cause permanent damage. Both diseases are major global concerns: tuberculosis for its high prevalence and mortality, and leprosy for its persistent global presence and high rate of neuropathic disability.

Risk factors for leprosy reactions in three endemic countries.

The objective of this study was to ascertain risk factors for complications (reactions or neuritis) in leprosy patients at the time of diagnosis in three leprosy-endemic countries. Newly diagnosed patients were enrolled in Brazil, the Philippines, and Nepal, and risk factors for reactions and neuritis were assessed using a case-control approach: "cases" were patients with these complications, and controls were patients without complications. Of 1,972 patients enrolled in this study, 22% had complications before treatment.

Mechanisms of nerve injury in leprosy.

All patients with leprosy have some degree of nerve involvement. Perineural inflammation is the histopathologic hallmark of leprosy, and this localization may reflect a vascular route of entry of Mycobacterium leprae into nerves. Once inside nerves, M.

IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy.

Background: Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines.

Compound heterozygous CORO1A mutations in siblings with a mucocutaneous-immunodeficiency syndrome of epidermodysplasia verruciformis-HPV, molluscum contagiosum and granulomatous tuberculoid leprosy.

Purpose: Coronin-1A deficiency is a recently recognized autosomal recessive primary immunodeficiency caused by mutations in CORO1A (OMIM 605000) that results in T-cell lymphopenia and is classified as T(-)B(+)NK(+)severe combined immunodeficiency (SCID). Only two other CORO1A-kindred are known to date, thus the defining characteristics are not well delineated. We identified a unique CORO1A-kindred.

The armadillo as a model for peripheral neuropathy in leprosy.

Leprosy (also known as Hansen's Disease) is a chronic infectious disease caused by Mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. Other than humans, nine-banded armadillos (Dasypus novemcinctus) are the only natural hosts of M. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium.

Mycobacterium leprae and Mycobacterium haemophilum co-infection in an iatrogenically immunosuppressed patient.

We present the case of a native Texan who was diagnosed with tuberculoid leprosy and later developed a cutaneous infection with M. haemophilum following iatrogenic immunosuppression. To our knowledge, there are no such reports of M.

Drug resistance in patients with leprosy in the United States.

Molecular drug susceptibility testing was performed on 39 US patients with leprosy. Of these, 2 had dapsone-resistant Mycobacterium leprae and 1 of these patients also had rifampin-resistant M. leprae.

The armadillo: a model for the neuropathy of leprosy and potentially other neurodegenerative diseases.

Leprosy (also known as Hansen's disease) is an infectious peripheral neurological disorder caused by Mycobacterium leprae that even today leaves millions of individuals worldwide with life-long disabilities. The specific mechanisms by which this bacterium induces nerve injury remain largely unknown, mainly owing to ethical and practical limitations in obtaining affected human nerve samples. In addition to humans, nine-banded armadillos (Dasypus novemcinctus) are the only other natural host of M.

What is the evidence that the putative Mycobacterium lepromatosis species causes diffuse lepromatous leprosy?

Han et al. have made a retrospective isolation of DNA from two patients with fatal Lucio's phenomenon. This DNA does have some molecular differences to M.

Evaluation of multi-drug therapy for leprosy in the United States using daily rifampin.

Objectives: To evaluate the occurrence of relapse of multibacillary leprosy after multi-drug treatment including daily rifampin.

Methods: A retrospective review was performed utilizing data from the National Hansen's Disease Program (NHDP) on patients with leprosy treated and followed from 1988-1997 who received multi-drug therapy including daily rifampin. The occurrence of relapse in this cohort was measured, and demographic data and various clinical variables were also gathered.