Bedaquiline Monotherapy for Multibacillary Leprosy.

Background: Standard multidrug therapy for leprosy may be associated with severe side effects, which add to the stigma and discrimination that affect persons with the disease. In addition, the threat posed by drug-resistant leprosy shows the need for alternative drug combinations and shorter, safer regimens of multidrug therapy.

Methods: In this open-label, proof-of-concept study conducted in Brazil, we assigned patients with previously untreated multibacillary leprosy to receive bedaquiline monotherapy for 8 weeks.

In vivo partial reprogramming by bacteria promotes adult liver organ growth without fibrosis and tumorigenesis.

Ideal therapies for regenerative medicine or healthy aging require healthy organ growth and rejuvenation, but no organ-level approach is currently available. Using Mycobacterium leprae (ML) with natural partial cellular reprogramming capacity and its animal host nine-banded armadillos, we present an evolutionarily refined model of adult liver growth and regeneration. In infected armadillos, ML reprogram the entire liver and significantly increase total liver/body weight ratio by increasing healthy liver lobules, including hepatocyte proliferation and proportionate expansion of vasculature, and biliary systems.

The Armadillo as a Model for Leprosy Nerve Function Impairment: Preventative and Therapeutic Interventions.

infection of peripheral nerves and the subsequent nerve function impairment (NFI), especially in response to reactional episodes, are hallmarks of leprosy. Improved treatments for -induced nerve injury are needed, as most if not all of the disability and stigma associated with leprosy arises from the direct or indirect effects of NFI. Nine-banded armadillos (), like humans, exhibit the full clinical spectrum of leprosy and extensive involvement of the peripheral nerves.

Mycobacterium leprae induces Schwann cell proliferation and migration in a denervated milieu following intracutaneous excision axotomy in nine-banded armadillos.

Nine-banded armadillos develop peripheral neuropathy after experimental Mycobacterium leprae infection that recapitulates human disease. We used an intracutaneous excision axotomy model to assess the effect of infection duration by M. leprae on axonal sprouting and Schwan cell density.

Detection and Monitoring of Infection in Nine Banded Armadillos () Using a Quantitative Rapid Test.

Leprosy is an infectious disease caused by with tropism for skin and peripheral nerves. Incessant transmission in endemic areas is still impeding elimination of leprosy. Although detection of infection remains a challenge in asymptomatic individuals, the presence of antibodies specific for phenolglycolipid-I (PGL-I) correlate with bacterial load.

Infection in Ticks and Tick-Derived Cells.

Leprosy is a zoonosis in the southern United States involving humans and wild armadillos. The majority of patients presenting with zoonotic strains of note extensive outdoor activity but only rarely report any history of direct contact with wild armadillos. Whether is transmitted to new vertebrate hosts through the environment independently or with the aid of other organisms, e.

Molecular epidemiology of leprosy: An update.

Molecular epidemiology investigations are notoriously challenging in the leprosy field mainly because the inherent characteristics of the disease as well as its yet uncultivated causative agents, Mycobacterium leprae and M. lepromatosis. Despite significant developments in understanding the biology of leprosy bacilli through genomic approaches, the exact mechanisms of transmission is still unclear and the factors underlying pathological variation of the disease in different patients remain as major gaps in our knowledge about leprosy.

Development of LepReact, a defined skin test for paucibacillary leprosy and low-level M. leprae infection.

The persistence of new leprosy cases in endemic areas such as India, Brazil, Bangladesh, and the Philippines has encouraged studies of chemoprophylaxis among contacts of patients. Epidemiological screening tools to enable early detection of infected individuals in endemic populations would be critical to target individuals most in need of intervention. Despite decades of attempts, however, there still are no tests available for the early detection of low-level infection with Mycobacterium leprae.

Serological and molecular detection of infection with Mycobacterium leprae in Brazilian six banded armadillos (Euphractus sexcinctus).

Leprosy was recognized as a zoonotic disease, associated with nine-banded armadillos (Dasypus novemcinctus) in the Southern United States of America in 2011. In addition, there is growing evidence to support a role for armadillos in zoonotic leprosy in South America. The current study evaluated twenty specimens of the six-banded armadillo (Euphractus sexcinctus), collected from rural locations in the state of Rio Grande do Norte (RN), Brazil for evidence of infection with Mycobacterium leprae.

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.

Erratum: Author Correction: LepVax, a defined subunit vaccine that provides effective pre-exposure and post-exposure prophylaxis of infection.

[This corrects the article DOI: 10.1038/s41541-018-0050-z.].

Differential growth of Mycobacterium leprae strains (SNP genotypes) in armadillos.

Leprosy (Hansen's Disease) has occurred throughout human history, and persists today at a low prevalence in most populations. Caused by Mycobacterium leprae, the infection primarily involves the skin, mucosa and peripheral nerves. The susceptible host range for Mycobacterium leprae is quite narrow.

LepVax, a defined subunit vaccine that provides effective pre-exposure and post-exposure prophylaxis of infection.

Sustained elimination of leprosy as a global health concern likely requires a vaccine. The current standard, BCG, confers only partial protection and precipitates paucibacillary (PB) disease in some instances. When injected into mice with the T helper 1 (Th1)-biasing adjuvant formulation Glucopyranosyl Lipid Adjuvant in stable emulsion (GLA-SE), a cocktail of three prioritized antigens (ML2055, ML2380 and ML2028) reduced infection levels.

The Armadillo (): A Witness but Not a Functional Example for the Emergence of the Butyrophilin 3/Vγ9Vδ2 System in Placental Mammals.

1-5% of human blood T cells are Vγ9Vδ2 T cells whose T cell receptor (TCR) contain a rearrangement and a comprising Vδ2-chain. They respond to phosphoantigens (PAgs) like isopentenyl pyrophosphate or (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMBPP) in a butyrophilin 3 (BTN3)-dependent manner and may contribute to the control of mycobacterial infections. These cells were thought to be restricted to primates, but we demonstrated by analysis of genomic databases that , and genes coevolved and emerged together with placental mammals.

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.

Gazelles, unicorns, and dragons battle cancer through the Nanotechnology Startup Challenge.

On March 4th, 2016, Springer's C office promoted the launch of the ( ). This innovation-development model is a partnership among our company, the Center for Advancing Innovation (CAI), MedImmune, the global biologics arm of AstraZeneca, and multiple institutes at the National Institutes of Health (NIH). "crowdsources" talent from around the world to launch startups with near-term, commercially viable cancer nanotechnology inventions, which were developed by the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Biomedical Imaging and Bioengineering (NIBIB).

Correction: Validation of qPCR Methods for the Detection of Mycobacterium in New World Animal Reservoirs.

[This corrects the article DOI: 10.1371/journal.pntd.

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.

Validation of qPCR Methods for the Detection of Mycobacterium in New World Animal Reservoirs.

Zoonotic pathogens that cause leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis complex, MTBC) continue to impact modern human populations. Therefore, methods able to survey mycobacterial infection in potential animal hosts are necessary for proper evaluation of human exposure threats. Here we tested for mycobacterial-specific single- and multi-copy loci using qPCR.

The armadillo as an animal model and reservoir host for Mycobacterium leprae.

Apart from humans, armadillos are the only known natural hosts of Mycobacterium leprae. They are well developed as hosts for in vivo propagation of M leprae and are advancing as models for studying the pathogenesis of leprosy and translational research. Armadillos are immunologically intact.

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.

Incidence of Hansen's Disease--United States, 1994-2011.

Hansen's disease (HD), or leprosy, is caused by the bacterium Mycobacterium leprae and is reportable in many states. It is a chronic disease affecting the skin and nerves, commonly presenting as pale or reddish skin patches with diminished sensation. Without treatment, it can progress to a severely debilitating disease with nerve damage, tissue destruction, and functional loss.

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.

PARK2 mediates interleukin 6 and monocyte chemoattractant protein 1 production by human macrophages.

Leprosy is a persistent infectious disease caused by Mycobacterium leprae that still affects over 200,000 new patients annually. The host genetic background is an important risk factor for leprosy susceptibility and the PARK2 gene is a replicated leprosy susceptibility candidate gene. The protein product of PARK2, Parkin, is an E3 ubiquitin ligase that is involved in the development of various forms of Parkinsonism.

Insights from animal models on the immunogenetics of leprosy: a review.

A variety of host immunogenetic factors appear to influence both an individual's susceptibility to infection with Mycobacterium leprae and the pathologic course of the disease. Animal models can contribute to a better understanding of the role of immunogenetics in leprosy through comparative studies helping to confirm the significance of various identified traits and in deciphering the underlying mechanisms that may be involved in expression of different disease related phenotypes. Genetically engineered mice, with specific immune or biochemical pathway defects, are particularly useful for investigating granuloma formation and resistance to infection and are shedding new light on borderline areas of the leprosy spectrum which are clinically unstable and have a tendency toward immunological complications.