Erythema nodosum leprosum (ENL) is a well-known immunological serious complication affecting lepromatous multibacillary leprosy patients. For a long time, ENL has been regarded as an immune complex-mediated disease or Arthus phenomenon. Recently, it has been reported that ENL was associated with high serum tumor necrosis factor-alpha (TNFa) levels, suggesting that this cytokine could also play a central role in the manifestations of ENL. Thalidomide (TH) and systemic steroids (S), both TNFa production inhibitors, are the two current effective drugs for the management of ENL. However, TH is rarely available in leprosy endemic countries, and its teratogenicity and neurotoxicity strongly limit its use. Moreover, the morbidity of S and the frequent steroid-dependence of ENL also create real therapeutic problems. Recently, the efficacy of pentoxifylline (PTX), which also inhibits in vitro and in vivo production of TNFa, has been suggested for ENL treatment. We report our experience on its use for the treatment of 15 leprosy patients suffering from a first ENL. attack. (11 cases), a chronic steroid-dependent ENL (3 cases) or chronic steroid- and thalidomide-dependent ENL (1 case). PTX has been given at 800 mg t.i.d, (2 cases) or 400 mg t.i.d. (13 cases) doses. The patients received PTX at the initiating dosage until complete clinical cure. At the end of ENL attacks, PTX was either abruptly stopped or tapered down over the next 4 months. In ten of 11 patients who developed ENL for the first time, the systemic symptoms and neuritic pains disappeared within one week; at three weeks, half of the patients were cured and the other half had striking clinical improvement; complete cure was obtained within 7 to 35 days (mean: 27 days). A relapse occurred within 2-3 months in the 5 patients, in which PTX was abruptly stopped. In contrast, no relapse occurred in the patients who benefited from decreasing doses of PTX. Recurrent ENL episodes also responded well to PTX. The 3 patients who had chronic steroid-dependent ENL failed to show any improvement after 3 to 6 weeks of PTX. In contrast, steroid therapy could be stopped in the steroid- and thalidomide-dependent patient. Our results confirm the action of PTX if it is slowly tapered down (4 months seem sufficient) and not abruptly to avoid relapses. As it is safe use, PTX could constitute the first line of ENL attack treatment.
Histoid leprosy is a particular variant of lepromatous leprosy presenting as cutaneous or subcutaneous nodular and/or plaque-like lesions arising form apparently normal skin. It is characterized histologically by spindle-shaped histiocytes in interlacing bundles and whorls, containing numerous intact and rod-shaped Mycobacterium leprae. It can occur de novo or secondary in patients treated for a long course by dapsone alone. We describe a case of lepromatous leprosy treated according to the national Moroccan protocol who developed histoid lesions during his treatment by dapsone. The patient responded well to fluoroquinolone, rifampicin and clofazimine, with however, the occurrence of erythema nodosum leprosum.
The bacteriological index (BI) of the skin smears is traditionally one of the important parameters of assessment of severity and of progress of leprosy under multidrug therapy. The present study reports on BI clearance among 578 multibacillary treated leprosy patients and the factors that influence this clearance. The patients were treated till smear negativity or for 2 years fixed duration and their skin smears periodically examined every 6 to 12 months till negativity (and even afterwards). We confirm that bacterial clearance is a slow process. The time taken for each log-unit decline in BI is between 13.6 to 24 months probably depending on initial BI level. The rate of smear negativity appears to be dependent on immune competence of the patients as reflected by a rapid BI decline in borderline BT-BB patients vis-à-vis BL-LL lepromatous patients both in the low and high BI group. Patients who had several episodes of ENL, took significantly longer time (63.7 months versus 53.5 months, p<0.0001) to become smear negative than those without ENL.
In this study we looked for the presence of antibodies to cardiolipin, cerebrosides, and whole lipids extracted from M. leprae, M. tuberculosis and M. habana, in the serum of patients with clinically cured lepromatous leprosy (sixteen) or tuberculosis (sixteen), 8 to 12 months after arresting the corresponding multi-drug therapy (MDT). Compared to healthy controls (sixteen), both leprosy and tuberculosis ex-patients had still significant levels of antibodies to the three mycobacterial lipids but no detectable levels of antibodies to cardiolipin or cerebroside lipids. Although leprosy and tuberculosis sera recognized the homologous mycobacterial lipids in a preferential fashion, all of them, on the average, reacted more strongly with the lipids of M. habana. This observation backs up, in a certain way, the proposition of using M. habana as a prospective vaccine for leprosy and tuberculosis.
Leprosy is believed to be transmitted only through human contacts. However, many anomalous observations had gradually accumulated which had weakened such beliefs. These are: only 1/3 rd cases of leprosy give a definite history of being transmitted from other known cases; life-long spouses, in whom only one has leprosy, seldom lead to leprosy to others; while MDT applied intensively in most leprosy endemic countries, could successfully reduce incidence of leprosy, however, simultaneously new cases arise unabated. Besides, a close look at animal leprosies also suggested a mode of transmission other than human-type contact. Thus, a search for alternative hypothesis led to the findings that leprosy bacillus (LB) could be a soil chemoautotroph and could facultatively live both in the human body and the soil which could serve as an alternative source of infection. Evaluation of accumulated evidences points to this possibility.
The performances of two Mycobacterium leprae specific serological assays namely: phenolicglycolipid-l-based enzyme-linked immunosorbent assay (PGL-ELISA) and a monoclonal antibody-based inhibition test (MAIT) were studied for there efficiency to detect M. leprae infection. As usual, both the tests were more sensitive to detect lepromatous leprosy patients than tuberculoid type of leprosy patients. Considering the efficiency to detect leprosy patients, the MAIT was slightly more sensitive and specific than PGL-ELISA. When the results of both assays are considered together, a better sensitivity (over the sensitivity of individual assay) was obtained while maintaining good enough specificity. These findings point out that a combinatorial approach for detection of M. leprae infection would be a better strategy to detect M. leprae infection. Hence, it may act as a better tool for measurement of bacterial load in the patients.
We report 2 new cases of immuno-allergic side-effects of rifampicin (RMP), occurred in leprosy patients treated by multidrug therapy. These cases illustrate the various features of this type of complication. In one case, the patient exhibited few days after restarting of RMP (600 mg daily), a typical flu syndrome associated to a thrombopenia. Previously, the patient had received discontinued RMP (300 mg, 3/5 days) that had to be stopped after 11 months for "general malaise" that in fact corresponded to a flu syndrome. The second patient developed a flu syndrome associated with a diffuse eczematous eruption one year after the onset of daily RMP (600 mg). Anti-RMP antibodies were detected only in the first case. The pathogenic mechanisms and the clinico-biologic features are discussed.
Primary neuritic leprosy (PNL) presents as a peripheral neuropathy with no visible skin patches and skin smears negative for acid fast bacilli. The pathogenesis of PNL is poorly understood. The aim of the study was to document the histological changes in the nerve, apparently normal skin and nasal mucosa in PNL and to study its significance to the pathogenesis of leprosy lesions. The study is based on a cohort of 208 PNL patients registered at the Schieffelin Leprosy Research and Training Centre, Karigiri. All patients had a nerve biopsy, 196 had a skin biopsy and 39 had a nasal mucosal biopsy. The findings reveal that PNL patients exhibit a spectrum of disease histologically in the nerve ranging from lepromatous to tuberculoid leprosy with a significant proportion (46%) manifesting a multibacillary leprosy histology. Findings in the apparently normal skin and nasal mucosa reveal that there are widespread changes due to leprosy in tissues such as the skin and nasal mucosa even when the disease appears clinically confined to a few nerves. PNL may be an early stage in the pathogenesis of the disease before the appearance of skin lesions. The number of nerves enlarged and lepromin status did not give any clue to the nature of underlying disease.
We report our experience of leprosy surgery in terms of feasibility and efficacy in a small hospital of bush in Madagascar during the period of September 1989 to January 1993. Operations of neurolysis, corrections of claw hands by the techniques of Lasso-Zancolli or Van Droogenbroeck, arthrodesis, resections and amputations have been performed. Our results suggest that at least a part of these surgical procedures may be performed by a non specialized medical team, taught on the premises. Thus, the cost of treatment will be low and accessible to more leprosy patients.
Leprosy is endemic in Madagascar and the diagnosis of leprosy is still done lately. Thus, many patients suffer from multiple and/or severe disabilities. Since a long time, many leprologists argue that surgery is necessary and useful in the treatment of these disabilities. We report the results of a retrospective study done in 25 patients reevaluated 2 to 7 years after surgery. Of these patients: 17 patients (68%) have success, 7 patients (28%) have a partial improvement and only 1 case (4%) had no benefit. These results are encouraging and suggest that surgery must be proposed more often to treat in leprosy disabilities.
Although leprosy became a curable disease after implementation of the Global Strategy for the Elimination of Leprosy (WHO), mutilations and deformities are still commonplace in endemic countries. Hence, it remains important to evaluate the prevalence rate and the risk factors of acral bone resorption in the multidrug therapy (MDT) era. A cohort of 105 newly-diagnosed adult multibacillary leprosy patients admitted for treatment between 1990-1992 was surveyed until 1999. Progression of bone resorption (BR) in cured leprosy patients was observed up to 8 years after release from MDT. Twenty three percent of the patients were found to have acral resorption. BR was found to be associated with male sex, grade of disability at diagnosis with other deformities and with the occurrence of four or more lepra reactions. Patient surveillance after release from MDT continues to be a necessary procedure in individuals with disabilities and recurrent or persistent reactions.
Leprosy is endemic in Madagascar. The authors report the results of an epidemiologic study performed between 1996 and 1998 in Farafanguna, localized in the South-Eastern of the country. During this period, 217 new cases have been diagnosed. Of the 130 cases included in the study, 69.23% were children aged lower than 15 years and 76.91% suffered from a multibacillary form. More than 50% of the cases belonged to a large family (6 persons or more) and at least one family case was found in more than 60% of cases. These results enhance the severity of the disease in the country and show the presence of multiple risk factors (promiscuity, family cases and multibacillary forms).
In order to develop objective criteria to monitor trends of therapeutic responses positivity of PCR signals and ATP assay methods has been compared in multibacillary (MB) leprosy patients. Biopsies from lesions of 95 BL/LL patients before and after one year of treatment with a new drug regimen comprising of conventional and newer drugs ofloxacin and minocycline have been studied. These biopsies were processed for bacillary ATP assay and PCR positivity for a 36 kDa gene target by earlier published methods. In the untreated patients bacillary ATP levels were detectable in all specimens and ranged from 0.02 to more than 36 pg/millions organisms. After one year of treatment ATP levels were not detectable in any of the 57 biopsies specimens available for analysis. However, PCR signals were detectable in 3 out of 57 biopsies. In two specimens signals were very weak detectable only by hybridization. It may be concluded that DNA based PCR assay may be useful in monitoring the trends of therapeutic responses in MB patients under treatment.
Anergy, or contrarily, Mitsuda-type responses towards 4 chemoautotrophic nocardioform antigens (CAN-Ags) and a control standard lepromin were tested in 73 LL, TT and borderline cases of leprosy. The antigens injected per patient varied from a maximum of 5 to a minimum of 2. Complete anergy to CAN-Ags was seen in 92/92 instances tested on 24 LL cases. The anergy was weakly modified or unmodified in 3 other LL cases which had been vaccinated before. Concurrent studies with the same antigens tested on 33 TT cases showed clear-cut, dose-dependent, Mitsuda-type late responses in 80/81 instances. The CAN bacteria, therefore, despite their origin from different unrelated leprous human, mouse footpad (MFP) and armadillo tissues, appeared to be identical with each other and also probably related to the leprosy bacillus, on the basis of these parameters.
A common problem of osteitis and septic arthritis is the recurrent bone infection after surgical debridement, a problem frequently encountered in patients with sequela leprosy. In these cases the authors propose the use of an ancient method of post surgical wound care based on the treatment with ordinary granulated sugar. The hyperosmolar climate created this way in the wounds inhibits the bacterial growth, enhances bacterial death and therefore permits the growth of granulation tissue in order to recover the debrided nude bones. At ILAD (Leprosy Institute of Dakar), 36 osteitis and septic arthritis were treated and healed during the last 2 years from March 1995 to March 1997 using this technic. All the wounds healed in the mean-time of 44 days. Only two of them needed a second debridement and healed afterwards. Up to now the method using ordinary sugar was applied in the treatment of infected wounds, eschars and postsurgical infections. Our experience shows that it also can be indicated to treat bone infections. This method is easy to apply also under often difficult field conditions and is very cheap.
