Systemic suppression of interferon-gamma responses in Buruli ulcer patients resolves after surgical excision of the lesions caused by the extracellular pathogen Mycobacterium ulcerans.

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is the third most common mycobacterial infection in immunocompetent humans besides tuberculosis and leprosy. We have compared by ex vivo enzyme-linked immunospot analysis interferon-gamma (IFN-gamma) responses in peripheral blood mononuclear cells (PBMC) from BU patients, household contacts, and individuals living in an adjacent M. ulcerans nonendemic region. PBMC were stimulated with purified protein derivative (PPD) and nonmycobacterial antigens such as reconstituted influenza virus particles and isopentenyl-pyrophosphate. With all three antigens, the number of IFN-gamma spot-forming units was reduced significantly in BU patients compared with the controls from a nonendemic area. This demonstrates for the first time that M. ulcerans infection-associated systemic reduction in IFN-gamma responses is not confined to stimulation with live or dead mycobacteria and their products but extends to other antigens. Interleukin (IL)-12 secretion by PPD-stimulated PBMC was not reduced in BU patients, indicating that reduction in IFN-gamma responses was not caused by diminished IL-12 production. Several months after surgical excision of BU lesions, IFN-gamma responses of BU patients against all antigens used for stimulation recovered significantly, indicating that the measured systemic immunosuppression was not the consequence of a genetic defect in T cell function predisposing for BU but is rather related to the presence of M. ulcerans bacteria.

Nerve damage in Mycobacterium ulcerans-infected mice: probable cause of painlessness in buruli ulcer.

Buruli ulcer is an emerging chronic painless skin disease found in the tropics and caused by Mycobacterium ulcerans; however, it remains unknown why the large and deep ulcers associated with this disease remain painless. To answer this question, we examined the pathology of BALB/c mice inoculated in the footpads with M. ulcerans African strain 97-107. On days 54 to 70 after inoculation, extensive dermal ulcers, subcutaneous edema, and numerous acid-fast bacilli were noted at the inoculate region. Nerve invasion occurred in the perineurium and extended to the endoneurium, and some nerve bundles were swollen and massively invaded by acid-fast bacilli. However, Schwann cell invasion, a characteristic of leprosy, was not observed. Vacuolar degeneration of myelin-forming Schwann cells was noted in some nerves which may be induced by mycolactone, a toxic lipid produced by M. ulcerans. Polymerase chain reaction analysis of microdissected nerve tissue sections showed positive amplification of M. ulcerans-specific genomic sequences but not of Mycobacterium leprae-specific sequences. Behavioral tests showed decrease of pain until edematous stage, but markedly ulcerated animals showed ordinary response against stimulation. Our study suggests that the painlessness of the disease may be partly due to intraneural invasion of bacilli. Further studies of nerve invasion in clinical samples are urgently needed.

Reação reversa com vasculites granulomatosas e lesões cutâneas necrosantes e ulcerativas / Reversal reaction with granulomatous vasculities and necrotizing cutaneous lesions

Um indivíduo com 49 anos de idade recebe o diagnóstico de Hanseníase Virchoviana sub-polar. Ele referiu, durante os prévios 11 anos, sintomas, principalmente neurológicos, característicos de hanseníase, mas este diagnóstico não foi definido nos serviços médicos que freqüentou. Após 6 meses de poliquimioterapia passou a apresentar neurites que foram tratadas como reação tipo 2. Em um último episódio apresentou febre, mal estar, mialgias e lesões necróticas e ulcerativas nos membros, nádegas, dorso, pavilhão auricular esquerdo. O aspecto clínico destas lesões era semelhante as lesões observadas no fenômeno de Lúcio e no Eritema nodoso necrosante. As biópsias mostram alterações da microvasculatura superficial, necrose epidérmica e dérmica, similares a estas reações, mas as alterações básicas são vasculites granulomatosas no derma profundo e tecido celular sub-cutâneo. Estes aspectos clínicos e histopatológicos são interpretados e discutidos como reação tipo 1 (reação reversa) com envolvimento vascular predominante.

Lucio leprosy with lucio phenomenon.

Leprosy is one of the commonly seen disease in any dermatology outpatient department in our country. India accounts for a major portion of the leprosy patients in the world. All types of the disease, such as tuberculoid, borderline, lepromatous, neuritic and indeterminate leprosy, are seen. However, "lucio leprosy" which is considered a special type of lepromatous leprosy characterised by diffuse involvement has not been reported from India. We are presenting here two cases of "lucio leprosy" with "lucio phenomenon", the lucio phenomenon being a special type of lepra reaction seen in lucio leprosy.

The predictive value of sensation testing in the development of neuropathic ulceration on the hands of leprosy patients.

The early detection of the loss of protective sensation in leprosy patients is vital if neuropathic ulceration and subsequent disabilities are to be avoided. The aim of this study was to find protective value of sensory thresholds in the hands of leprosy patients. Thresholds for touch-pressure, vibration and temperature were assessed in areas on leprosy-affected hands near ulcers or ulcer scars (LU-group), in areas without lesions (LN-group), and in controls (N-group). Semmes-Weinstein monofilaments were used for testing the touch-pressure threshold (PST), a biothesiometer for the vibration threshold (VST) and a Thermo Sensation Tester for the temperature threshold (TST). The distribution of ulcers was about equal on palmar and dorsal aspects of the hands. In the LU-group there was a negative response to SWF of 2.0 g in all patients, while 74% could feel the 2.0 g in LN-areas and in N-areas 100% could detect the 2.0 g SWF. In the LU-group about 11% felt 8 V VST, in the LN-group about 60% and in the N-group 89%. Testing temperature sensation was given up prematurely because the results in controls were unsatisfactory. Both palmar and dorsal sides of the hands should be tested for sensation. The thresholds for protective sensation are 2.0 g SWF and 8 V for vibration sense. It is recommended that Semmes-Weinstein monofilaments should always be used for early detection of loss of protective sensation.

An evaluation of the Semmes-Weinstein 6.10 monofilament as compared with 6 nylon in leprosy patients.

In a previous study Birke and Sims (1986) identified the 5.07 (10 y) Semmes-Weinstein monofilament, as the most useful tool, in measuring protective sensation in the sole of the foot of leprosy patients. This study has demonstrated that the standard 6 Nylon being used in Karigiri, is as good as the monofilament, in assessing protective sensation in leprosy patients. However there is a need for standardising procedures for measuring sensory loss in leprosy patients.

[Frequency of the association of perforating plantar leprotic lesions and truncal involvement of the posterior tibial nerve]. / Fréquence de l'association entre les maux perforants plantaires lépreux et l'atteinte tronculaire du nerf tibial postérieur.

This study was performed to determine the electrophysiological status of the posterior tibial nerve and its muscular innervation in patients both with and without plantar ulcers without osteitis. In both cases, motor distal latencies remained normal, but the denervation of the plantar muscles was significantly more important in patients with ulcers. These results show that axonal degeneration is predominant in leprous neuritis affecting the tibial nerves. Neurolysis was performed in twelve patients in the retromalleolar part of the tibial nerve. All patients have recover from their ulcers, but no improvement of their electrophysiological parameters was observed.