[Randomized controlled trial of medical and medico-surgical treatment of Hansen's neuritis]. / Essai comparé randomisé du traitement médical et médico-chirurgical des névrites hanséniennes.

The aim of the study was to compare the results of the medical treatment alone and of the medico-surgical treatment on leprous neuritis. The patients were followed-up during 2 years, with regular neurological evaluations. The statistical study was performed using the Tukey test. Ninety-three nerves (ulnar, median, common peroneal and posterior tibial) with a deficit of less than 6 months duration have been studied in 31 leprosy patients. All the patients were treated by steroids but in some of them a nerve surgical decompression was performed. An improvement of the sensitive and motor deficit was observed in both groups. No significant statistical differences appeared between the 2 groups according to the nerve involved, the duration of the deficit, the form of leprosy and the type of antibacillary treatment. However, the medico-surgical treatment had a significant better result on pain and on major but incomplete nervous involvement. This study included a limited number of nerves, thus, it would be useful to perform others randomized assays to better define the indications of surgical decompression in the management of leprous neuritis.

[Evaluation of the elimination of leprosy in Burkina Faso]. / Evaluation de l'élimination de la lèpre au Burkina Faso.

During May and June 1997, we conducted a rapid survey on leprosy prevalence in 30 villages. It was to assess reaching of the leprosy elimination threshold (one case per 10,000 inhabitants) in Burkina Faso. We drew lots for the villages in ten provinces among which five had the highest prevalence rates of leprosy in 1996 and five had the lowest prevalence rates. We added a leprosy elimination monitoring to the survey. This monitoring consisted of visits to the health centers covering the 30 villages. We interviewed and clinically examined 33 cases of leprosy in treatment in those health centers. We found fifty-one patients of leprosy in visited villages. The prevalence rate of leprosy (6.74 per 10,000 inhabitants) was twice higher than the prevalence rate registered in the same villages. We detected 28 new cases of leprosy during the survey. Proportion of hidden cases of leprosy were 54.9%. We estimated geographical coverage of MDT at 75% in the 10 provinces. Eight of the 27 visited health centers (29.6%) did not get sufficient supply. The cure rate has fallen from 93 to 73 per cent between 1992 and 1997. Our results show that leprosy elimination threshold is not reached in Burkina Faso. Leprosy control activities that were declining during the last five years need to be reinforced.

[How to detect neuropathy in leprosy]. / Comment dépister la neuropathie hansenienne?

In leprosy, the early detection of peripheral nerve damage is essential for the prevention of disability. To date, there is no consensus on what is the best clinical test to reveal such abnormalities. In this prospective study we examined the effectiveness of five clinical tests to assess radial cutaneous nerve (RCN) damage (the most frequently involved). Light touch was assessed by two nylon threads (based on the Semmes-Weinstein monofilaments testing technique) bent on the skin at a pressure of 0.5 (N. 4 nylon) and 0.2 gram (N. 5 nylon). Pinprick and cooling sensations were examined by a needle and a drop of ether. The nerve thickness was assessed by palpation. Sensory findings were then compared to sensory nerve conduction values of the RCN and a sensitivity analysis was performed. The patient group consisted of 108 consecutive new leprosy sufferers (138 RCN) who attended the Institut de Léprologie Appliquée de Dakar during one year. Diagnosis and classification were based on Ridley and Jopling's criteria (clinical examination, skin smears and biopsy). Normal values were determined among 22 healthy subjects (44 RCN). The best tests in term of sensitivity were palpation (.60), N. 5 nylon (.65) and N. 5 + palpation (.79). Their positive predictive values were .84 (palpation), .94 (N. 5 nylon) and .83 (N. 5 + palpation). The best tests in term of area under the curve were palpation (.66), N. 5 nylon (.71) and N. 5 + palpation (.78). The results remain the same for the lepromatous or tuberculoid leprosy patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Segmental ulnar nerve conduction in Hansen's disease]. / Les vitesses de conduction motrices cubitales étagées dans la maladie de Hansen.

In leprosy, ulnar neuritis is considered to be selectively localised at the elbow and is often treated by surgical decompression when pain and/or neurological deficit occurs. The aim of this prospective study is to assess the prevalence, localisation and severity of ulnar nerve damage in leprosy. Motor nerve conduction velocity (MNC) was measured at 3 different segments: arm, elbow and forearm, and was expressed both in meters/second and percentage of the mean normal values found in our laboratory or as reported in other studies. The patient group consisted of 123 consecutive new leprosy sufferers (228 ulnar nerves only) who attended the Institut de Léprologie Appliquée de Dakar over the period of one year. Diagnosis and classification were based on Ridley & Jopling's criteria, including skin and nerve biopsy. Mean MNC was reduced by 13.5 m/s at the arm, 19.8 m/s at the elbow and 7.8 m/s at the forearm as compared to the mean normal values. Increased distal latency as an isolated finding was rare (0.9%). Mean MNC was more reduced in the BL, LL (lepromatous) than in the TT, BT (tuberculoid) subgroups, despite similar disease durations (22.3 +/- 18.7 months and 24.2 +/- 26.4 months respectively (n.s.). Using different normal MNC values did not affect the conclusion: we did not see any selective slowing of ulnar MNC at the elbow suggesting that nerve damage is not primarily related to mechanical factors.

Prevalence of antibodies to hepatitis C virus among patients with leprosy in several African countries and the Yemen.

The prevalence of anti-HCV was determined in 1,309 leprosy patients and a control group of 1,469 subjects from 6 sub-Saharan African countries and the Yemen. Sera found positive by an initial second generation ELISA were subjected to 3 additional confirmatory tests. The anti-HCV prevalence in leprosy patients (7.1%) was significantly higher than in the control group (2.6%). HCV seroprevalence increased with age in both the control and leprosy groups. No statistically significant difference could be found between anti-HCV prevalence and the several clinical forms of leprosy among patients. The results of this study indicate a high degree of exposure or chronic carriage of hepatitis C among leprosy patients.

IgG response to purified 65- and 70-kDa mycobacterial heat shock proteins and to antigen 85 in leprosy.

IgG antibody response to mycobacterial heat-shock proteins (hsp) (the 70-kDa antigen from Mycobacterium tuberculosis and M. bovis BCG; the 65-kDa antigen from M. leprae and M. bovis BCG) and to the fibronectin-binding antigen 85 from M. bovis BCG was analyzed in a dot-blot assay in plasma from leprosy patients and their contacts. Most plasma--whatever the status of the subjects--reacted to the hsp 70; 8 of 9 (89%) of paucibacillary patients recognized the 65 mycobacterial hsp but only 2 of 9 (22%) recognized the antigen 85. In contrast, 12 of 12 (100%) of multibacillary patients reacted with the antigen 85 and only 4 of 12 (33%) reacted to the hsp 65 from M. leprae. On the one hand, 7 of 25 (28%) of the lepromin-positive contacts and 2 of 9 (22%) of the lepromin-negative contacts recognized the antigen 85. On the other hand, 11 of 25 (44%) of the lepromin-positive contacts but only 1 of 9 (11%) of the lepromin-negative contacts reacted to the hsp65 from M. leprae. Finally, very few (10%) of the lepromin-positive controls showed a positive reaction to the M. leprae 65-kDa antigen, the BCG 65-kDa antigen, and the 85-kDa antigen of BCG. Thus, differences in binding to the hsp65 from M. leprae and to antigen 85 could be helpful in distinguishing different forms of the disease.

T-cell stimulation with purified mycobacterial antigens in patients and healthy subjects infected with Mycobacterium leprae: secreted antigen 85 is another immunodominant antigen.

Peripheral blood leucocytes from 9 paucibacillary and 12 multibacillary leprosy patients, from 18 healthy controls and from 34 healthy leprosy contacts were stimulated with three mycobacterial heat shock proteins with respective molecular weights of 70, 65 and 18 kDa and with the secreted 30-32 kDa protein, also called antigen 85. Antigen 85 was found to be the most powerful T-cell antigen (as measured by lymphoproliferation and IFN-gamma secretion), eliciting a positive response in all (100%) paucibacillary patients and in all lepromin-positive controls and contacts. The three heat shock proteins (hsp) were less active T-cell stimuli. Reactivity to the 70 kDa hsp was found in only 44% of the paucibacillary patients, in 80% of the lepromin-positive controls and in 60% of the lepromin-positive leprosy contacts. The 65 kDa hsp stimulated T cells in 89% of the paucibacillary patients and in 80% of the lepromin-positive controls and contacts. Responsiveness to the 18 kDa hsp, finally, was clearly more frequent in tuberculoid leprosy patients (78%) than in lepromin-positive controls (40%) or lepromin-positive leprosy contacts (4%). T-cell reactivity of 8 lepromin-negative controls, of 9 lepromin-negative contacts and of 12 multibacillary leprosy patients was low to all the antigens tested. Although proliferative and IFN-gamma responses were generally closely related, some subjects demonstrated a dissociation of these two immune parameters. Our data confirm previous findings on the powerful T-cell stimulatory properties of antigen 85 during M. leprae infection and suggest that this antigen is indeed a potentially protective T-cell immunogen.

Leprosy reversal reaction in HIV-positive patients.

We report two cases of leprosy in HIV-infected patients who, by their clinical, histological and immunological features, enhance the evidence that HIV-positive leprosy does not differ from nonHIV-positive leprosy. Moreover, extensive studies of reversal reactions in HIV-positive patients might be of great interest in determining the exact pathogenesis of this leprosy reactional state.

The major secreted antigen complex (Ag 85) from Mycobacterium bovis bacille Calmette-Guérin is associated with protective T cells in leprosy: a follow-up study of 45 household contacts.

T cell proliferation and interferon (IFN)-gamma secretion were analyzed in 45 leprosy contacts stimulated with antigen 85 (Ag85), the major culture filtrate antigen from Mycobacterium bovis bacille Calmette-Guérin. All 14 Mitsuda reaction-positive contacts reacted to Mycobacterium leprae and Ag85. Three Mitsuda reaction-negative contacts reacted weakly to M. leprae and Ag85. The other 28 Mitsuda reaction-negative contacts did not react to M. leprae, but 9 reacted to Ag85. Thirty-four contacts were retested 16 months later. Eleven contacts initially positive by the Mitsuda test remained lepromin positive and reactive to M. leprae and Ag85. Fourteen contacts initially negative by the Mitsuda test converted, and all reacted in vitro to M. leprae and Ag85. Finally, 9 contacts remained Mitsuda test-negative, and 7 were unreactive to Ag85. In vitro reactivity to Ag85 at baseline in Mitsuda test-negative contacts was associated with subsequent conversion to lepromin reactivity in 7 of 9 subjects. These data suggest that reactive T cells against Ag85 develop very early during M. leprae infection and that Ag85 is a potentially protective T cell immunogen.

IL-6 production in response to purified mycobacterial heat-shock proteins and to antigen 85 in leprosy.

IL-6 production was examined in PBMC cultures from healthy leprosy contacts and from leprosy patients stimulated with the purified mycobacterial 18-, 65-, and 70-kDa heat-shock proteins (hsp) and the secreted fibronectin-binding antigen 85 (Ag85). In lepromin-negative contacts, the 70-kDa hsp was the only antigen capable of eliciting significant IL-6 production. In lepromin-positive contacts, Ag85, the 65- and the 70-kDa hsp induced substantial IL-6 titers. IL-6 levels induced with the 70-kDa antigen were about fourfold higher than with the 65-kDa hsp or with Ag85. The 18-kDa antigen did not induce any IL-6 in these healthy contacts. PBMC from tuberculoid leprosy patients produced even more elevated levels of IL-6, and PBMC from lepromatous leprosy patients produced extremely high levels of IL-6. All antigens were capable of inducing IL-6 in leprosy patients. Highest levels were found in cultures stimulated with the 65-kDa hsp, and lowest levels were in cultures stimulated with the 18-kDa hsp.

Anti-peripheral nerve antibodies in leprosy patients recognize an epitope shared by the M. leprae 65 kDa heat shock protein.

Binding of leprosy sera to peripheral nerve from different species (mouse, guinea pig and rabbit) was evaluated by ELISA. A majority of sera, whatever the clinical form of leprosy, bind to these antigens. Absorption with Mycobacterium bovis BCG demonstrated that these antibodies recognize cross-reactive epitopes between peripheral nerve and mycobacteria. In immunoblot analysis, both leprosy patient sera and a monoclonal antibody directed at the 65 kDa heat shock protein of M. leprae were shown to react with a heat-shock 67-68 kDa sciatic nerve protein. Binding of the monoclonal antibody to this sciatic nerve antigen was prevented by incubation with lepromatous patient sera, showing that some peripheral nerve epitopes recognized by patient antibodies are shared by the 65 kDa heat shock protein of M. leprae.