Chemoprophylaxis of leprosy in the southern Marquesas with a single 25 mg/kg dose of rifampicin. Results after 10 years.

In 1988, a programme of leprosy chemoprophylaxis, employing a supervised, single 25 mg/kg dose of rifampicin, was implemented in the Southern Marquesas Islands. Of the 2786 inhabitants, 2751 (98.7%) were treated. In addition, 3144 South Marquesans living elsewhere in French Polynesia were administered the same chemoprophylaxis. During the following 10 years, seven leprosy patients were detected among those who had been administered chemoprophylaxis. Of these, two were very likely missed cases of leprosy, and cannot be considered a failure of chemoprophylaxis. The epidemiometric projection model, based on cases of leprosy observed in the Southern Marquesas during the 20 years preceding implementation of the programme, predicted that 17 leprosy cases could be expected in the South Marquesan population if no chemoprophylaxis were given. In fact, only five cases were detected in the treated population, a number significantly smaller than 17, suggesting that the chemoprophylaxis was 70% effective, assuming that no change of detection rate would have occurred without chemoprophylaxis. However, during the 10 years following implementation of the chemoprophylaxis programme, the detection rate in the Polynesian population that was not administered chemoprophylaxis declined by about 50%. Therefore, the effectiveness of the chemoprophylaxis was only 35-40%.

[How does one treat the osteitis and osteoarthritis of the extremities in older leprosy patients using granulated table sugar?]. / Comment guérir les ostéites et ostéo-arthrites des extrémités des anciens malades de la lèpre par le sucre cristallisé alimentaire?

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.

[Can plantar ulcers associated with leprosy be treated in the field. Results of experience in Senegal]. / Peut-on soigner les maux perforants plantaires des anciens malades de la lèpre sur le terrain? Résultats d'une expérience au Sénégal.

The introduction of a program for the treatment of plantar ulcers (PU) in field conditions in Senegal was studied. The program was complementary to the Health Education and Protective Footwear to Prevent Disability (POD) initiatives within the Senegalese anti-leprosy program. The wound care given in health centers was coded and simplified. Access to hospitals was made easier for those patients requiring surgery. More than 30% of patients with PU were treated each year, with a mean of 62% cured. An increasing number of leprosy patients have been admitted to regional hospitals for surgery. Never before have patients with signs of leprosy had access to general hospitals. This study emphasizes the need for regular supervision of the individuals treating wounds.

Field trial on efficacy of supervised monthly dose of 600 mg rifampin, 400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first results.

In 1995, a field trial was implemented in Senegal in order to evaluate the efficacy of a regimen based on the monthly supervised intake of rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg to treat leprosy. During the first year of the trial, 220 patients with active leprosy (newly detected or relapsing after dapsone monotherapy) were recruited: 102 paucibacillary (PB) (60 males and 42 females) and 118 multibacillary (MB) (71 males and 47 females). All of them accepted the new treatment (none requested to be preferably put under standard WHO/MDT), no clinical sign which could be considered as a toxic effect of the drug was noted, and none of the patients refused to continue treatment because of any clinical trouble. The compliance was excellent: the 113 patients (PB and MB) detected during the first 6 months of the trial have taken six monthly doses in 6 months, as planned. The rate of clearance and the progressive decrease of cutaneous lesions was satisfactory. Although it is too soon to give comprehensive results, it should be noted that no treatment failure was observed in the 56 PB patients who have completed treatment and have been followed up for 6 months. The long-term efficacy of the new regimen is to be evaluated on the rate of relapse during the years following the cessation of treatment. If that relapse rate is acceptable (similar to that observed in patients after treatment with current standard WHO/ MDT), the new regimen could be a solution to treat, for instance, patients very irregular and/or living in remote or inaccessible areas since no selection of rifampin-resistant Mycobacterium leprae should be possible (a monthly dose of ofloxacin and minocycline being as effective as a dose of dapsone and clofazimine taken daily for 1 month). Nevertheless, until longer term results of this and other trials become available, there is no justification for any change in the treatment strategy, and all leprosy patients should be put under standard WHO/MDT.

[Should biopsy be done on the sensory branch of the radial nerve in leprosy patients? Apropos of 112 cases]. / Doit-on pratiquer des biopsies de la branche sensitive du nerf radial chez les malades lépreux? A propos de 112 cas.

Biopsies of the superficial sensory branch of the radial nerve are contested. Some authors mention it to be simple and without harm, but others are formally against this procedure. At ILAD, 274 biopsies were made between 1986 to 1992. We present a review of 112 leprosy patients for whom biopsy was done. On 112 reexamined patients, we observed 2 benign neuroma, hence 2%. The comparison of nerve function before biopsy and after, of 63 of the 112 patients, reexamination shows no significant modification of the functional score. Given even the occurrence of benign neuroma in only 2% of the cases, the authors do not recommend the biopsy of the superficial sensory branch of the radial nerve. For research purposes on neuritis in leprosy, as well as to assure diagnosis in primary neuritic leprosy, we propose the biopsy of the sensory branch of the musculo cutaneous nerve at elbow level.

[Simplification and codification of treatment for leprous plantar ulcers]. / Simplification et codification des soins aux maux perforants plantaires lépreux.

Practically leprous plantar ulcers (PU) are difficult to treat and heal under field condition. Considering the important number of patients showing a PU, the directors of national leprosy control programmes are determined, within the programmes on prevention of disabilities (POD), to treat the PU in the field. Therefore it appears to be essential to codify and simplify their treatment thus enabling it to be effective. The healing of PU being the only criteria of effectiveness of the technique. Four clinical stages were defined, each corresponding to a precise way of treatment using only essential and basic products at low cost. During the trainings about the treatment techniques and attitudes much emphasize is given on the discharge of the PU, on the trimming of the wound and on the products to use according to PU's evolutionary stage.

Pseudoepitheliomatous hyperplasia in trophic ulcers in leprosy patients. A 28-case study.

Between 1984 and 1993, pseudoepitheliomatous hyperplasia developing in chronic ulcers were observed in 28 former Senegalese leprosy patients, which amounts to an annual frequency of 1.9 per 1000 ulcers. Correct diagnosis could only be made by histopathological examination of specimens taken from the depth of the lesion. Amputation was carried out on 17 patients and local excision on the other 10. Recurrence of growth was observed in 8 of the 10 patients treated by excision; in all of these 8 cases below knee amputation had to be subsequently performed. From our experience, it may be assumed that local excision should be carried out only in the case of small tumours. Since the aim of surgical procedure is to allow the patient to have physical autonomy, below knee amputation, followed by adaptation of prosthesis, should be the procedure chosen in the other cases.

[External canthopexy using the Edgerton-Montandon procedure in lagophthalmos of leprosy patients. Technique and indications. Apropos of 30 cases]. / La canthopexie externe selon le procédé d'Edgerton-Montandon dans les lagophtalmies des malades de la lèpre. Technique et indications. A propos de trente cas.

This paper deals with the results observed in 21 ancient leprosy patients suffering from lagophthalmos (13 of whom suffered from bilateral lagophthalmos) and treated by the Edgerton-Montandon surgical procedure which associates lateral canthopexy and tarsorraphy. Eighteen of the 21 treated patients were reviewed at one month after the procedure and, overall, results could be evaluated for 30 eyes. Improvement was noted in all of the 30 eyes and, globally, the residual palpebral fissure (during voluntary closing of the eyes by the patient) decreased from 6.7 mm before the procedure to 1.8 after the procedure. The following recommendations may be proposed. For young patients with intact corneal sensation, the Gillies procedure remains the procedure of choice to correct lagophthalmos. For older patients with corneal anesthesia, at high risk of blindness, the Edgerton-Montandon procedure should be recommended.

[Tumoral proliferations in chronic plantar ulcers: how to treat?]. / Proliférations tumorales développées sur maux perforants plantaires: quelle attitude thérapeutique?

Between 1983 and 1994, 66 Senegalese leprosy patients were seen for cauliflower growths developed in chronic plantar ulcer (CPU), (2 patients had each 2 tumors). 68 biopsies for pathological examination were taken: the diagnosis of squamous cell carcinoma was effectively made in 39 cases (38 patients) and that of pseudo-epitheliomatous hyperplasia in the remaining 29 cases (28 patients). The mean annual frequency of cauliflower growths was 0.45 per 100 CPU. Among these tumors, the percentage of carcinoma was 57%. Of the 38 patients with a carcinoma, 5 refused amputation and all of them died. The 33 others were amputated and of these 8 died as a direct result of their carcinoma (24%). In the case of the 28 patients with hyperplasia, amputation was carried out on 18 patients and local excision on 10. In the months following the operation 8 recurrences were observed in 10 of the patients on whom excision had been carried out. These recurrences were treated by amputation. This gives a total of 93% of amputations in the cases of hyperplasia. These facts lead as to conclude that at least in countries where pathological examination is not available below knee amputation is the most reasonable action to take in the proliferative tumors developed on a CPU.

Fibronectin-binding antigen 85 and the 10-kilodalton GroES-related heat shock protein are the predominant TH-1 response inducers in leprosy contacts.

Peripheral blood mononuclear cells from 27 healthy leprosy contacts were analyzed for lymphoproliferation and TH-1 cytokine secretion (interleukin-2 and gamma interferon) in response to heat shock proteins with molecular masses of 65, 18, and 10 kDa from Mycobacterium leprae and the 30-32-kDa antigen 85 (Ag 85) from Mycobacterium bovis BCG. Cells from 18 and 19 of 19 lepromin-positive contacts proliferated or produced TH-1 cytokines in response to the M. leprae 10-kDa protein and to Ag 85, respectively. Limiting-dilution analysis for two lepromin-positive contacts indicated that about one-third of M. leprae-reactive T cells displayed specificity to the M. leprae 10-kDa protein and Ag 85. The M. leprae 65- and 18-kDa proteins were less potent TH-1 response inducers: gamma interferon and interleukin-2 could be measured in 14 and 19 lepromin-positive contacts, respectively. In contrast, very low or undetectable proliferative and cytokine responses were found for 8 lepromin-negative contacts. Our data demonstrate that the fibronectin-binding Ag 85 and the 10-kDa GroES homolog are powerful mycobacterial TH-1 response inducers in the vast majority of lepromin-positive contacts and suggest that they might be valuable candidates for a future subunit vaccine.

[Results obtained by a mobile handicap-prevention unit at the Institut de Léprologie de Dakar]. / Résultats obtenus par une équipe mobile de prévention des invalidités à l'Institut de Léprologie de Dakar.

Of 584 leprosy patients known at the Institut de Léprologie Appliquée de Dakar because they suffered a nerve lesion with or without chronic plantar ulcer (CPU), 242 (41%) could be followed-up during a mean period of time of 8.2 years (range: 5 and 10 years) by the means of the mobile disability prevention team (health education, medical care and shoe workshop). Every two months a visit of the patients, at their home town, was organized, with the purpose to assess whether they could actually put into practice the foot and hand as having been trained for. At the same time, further advice and encouragement were given to the patients. Adapted footwear was brought to the patient, at reduced fee, the foot prints and special moulds having been taken during the previous visit. The local health worker were responsible for light surgical cares. Among the 242 followed-up patients: of 107 without CPU at beginning, 90 (84%) remained so, of 135 with CPU at beginning, 57 (42%) were cured, of 135 with CPU at beginning, 74 (55%) remained stable (no worsening), the last 21, of whom 17 showed severe foot deformities but without CPU, worsened (all presented one or more CPU at the last control). Of the 242 patients, 221 (91%) remained stable or showed substantial improvement. Therefore, it must be emphasized that careful follow-up of patients is essential to insure the improvement or care of CPU as well as to prevent the onset, worsening or reappearance of CPU. Such follow-up must consist of cares, health education and special shoe wearing.

[The frequency of the appearance of perforating foot ulcers in patients with Hansen's disease as a function of treatment with disulone alone or with polychemotherapy]. / Fréquence d'apparition de maux perforants plantaires chez des malades hanséniens en fonction du traitement par disulone seule ou polychimiothérapie.

Between 1986 and 1989, in 5 departments of Senegal, 436 new cases of leprosy were detected, of whom 225 were put under dapsone monotherapy and 211 under multidrug therapy (MDT). Of them, 190 could be followed-up during 2 years by means of annual bacteriological and clinical examination, including neurological assessment. In 2 years, the onset of 10 (5.3%) chronic plantar ulcers (CPU) was observed: 4 (4%) among the 99 patients under dapsone monotherapy and 6 (6.6%) among the 91 under MDT (no significant difference). Of the 10 CPU, 3 (2%) appeared among the 149 patients without any disability at detection while 7 (17%) were observed among the 41 others who presented a grade 1 disability at detection (p < 0.01). Of the 6 CPU appeared in the patients under MDT, 5 (22%) were observed among the 23 who presented a grade 1 disability at detection and 1 (1.5%) among the 68 who did not (p < 0.01). This difference was not noted in the patients under dapsone monotherapy. Our results need to be confirmed by other studies including a higher number of patients followed-up during a longer period of time. Nevertheless, they suggest that MDT could prevent the onset of CPU, but only in patients without any disability at detection. Therefore, they reemphasize the importance of early detection of the disease in leprosy control programmes.

T-cell-epitope mapping of the major secreted mycobacterial antigen Ag85A in tuberculosis and leprosy.

Lymphoproliferation and gamma interferon (IFN-gamma) secretion in response to 28 overlapping 20-mer synthetic peptides covering the complete sequence of the mature (295-amino-acid) 85A component of the major secreted, fibronectin-binding antigen 85 complex from Mycobacterium tuberculosis and Mycobacterium bovis BCG (MTAg85A) was examined by using peripheral blood mononuclear cell (PBMC) cultures from healthy tuberculin- and lepromin-positive volunteers and from patients with tuberculosis and leprosy. Peptide recognition was largely promiscuous, with a variety of human leukocyte antigen haplotypes reacting to the same peptides. PBMC from all tuberculin-positive subjects reacted to Ag85, and the majority proliferated in response to peptide 6 (amino acids 51 to 70), peptides 13, 14, and 15 (amino acids 121 to 160), or peptides 20 and 21 (amino acids 191 to 220). PBMC from tuberculosis patients demonstrated a variable reactivity to Ag85 and its peptides, and the strongest proliferation was observed against peptide 7 (amino acids 61 to 80). MTAg85A peptides were also recognized by PBMC from healthy lepromin-positive volunteers and paucibacillary leprosy patients (again in a promiscuous manner), but despite a 90% homology between the 85A proteins of M. leprae and M. tuberculosis, the peptides recognized were different. PBMC from lepromin-positive healthy contacts reacted against peptide 2 (amino acids 11 to 30), peptide 5 (amino acids 41 to 60), and peptides 25 and 26 (amino acids 241 to 270). PBMC from paucibacillary patients reacted preferentially against peptide 1 (amino acids 1 to 20) and peptide 5. Multibacillary patients were not reactive to Ag85 or the MT85A peptides. IFN-gamma production was generally detected simultaneously with positive lymphoproliferative responses, although peptide 1 mostly stimulated proliferation and peptides 27 and 28 mostly elicited an IFN-gamma response. In conclusion, regions 41 to 80 and 241 to 295 demonstrated powerful and promiscuous T-cell-stimulatory properties, resulting in proliferative responses and IFN-gamma secretion, respectively, in the majority of reactive subjects tested in this study. These results could be of value in the development of a subunit vaccine for tuberculosis and leprosy.

Rate of relapse in multibacillary patients after cessation of long-course dapsone monotherapy supplemented by a final supervised single dose of 1500 mg of rifampin.

When multidrug therapy was implemented in Senegal, 406 multibacillary (MB) patients who had been treated for more than 10 years by dapsone alone, and who had become clinically inactive and skin-smear negative, were released from treatment. Of these 406 patients, 298 were given a supervised single dose of 1500 mg of rifampin. Subsequently, 302 of them (229 who had been given rifampin and 73 who had not) were followed up by means of annual clinical and bacteriological examinations. Of the former 229 followed up for a mean period of 4.9 years, 34 patients relapsed (22 males and 12 females), giving a crude relapse rate of 15% and an overall risk of relapse of 3.1 per 100 patient-years. Of the latter 73 followed up for a mean period of 2.4 years, 5 relapsed (4 males and 1 female), giving a crude relapse rate of 6.8% and an overall risk of relapse of 2.9 per 100 patient-years. Such results, which are in agreement with those of a similar study conducted recently in Mali, indicate that the intake of a single dose of 1500 mg of rifampin by MB patients when they are released from long-course dapsone monotherapy does not result in a decrease of the relapse rate. Therefore, MB patients who have been treated with dapsone alone, even for long periods, should be put under multidrug therapy prior to their release from control.

T cell reactivity against antigen 85 but not against the 18- and 65-kD heat shock proteins in the early stages of acquired immunity against Mycobacterium leprae.

T cell proliferation and interferon-gamma (IFN-gamma) production of peripheral blood mononuclear cells (PBMC) from 20 household contacts were tested against the 18- and 65-kD heat shock proteins from Mycobacterium leprae (ML18 and ML65 respectively) and antigen 85 from Myco. bovis bacille Calmette-Guérin (BCG) (Ag 85) during a 12-months follow-up study. Among the eight contacts that became positive, eight showed positive reactivity against Ag 85, 5/8 against ML65 and 4/8 against ML18 at the end of the study. Of the 16 contacts who were lepromin-positive either at first or second testing, all responded to Ag 85, 11 to ML 65, but only eight reacted to ML18 antigen. Contacts who were lepromin-positive at first testing developed responses to ML18 only at second testing. In contrast, among the four contacts that remained lepromin-negative during the follow up, three proliferated to Ag 85 either at first or second testing, but only one produced IFN-gamma against Ag 85 at the end of the study. These results demonstrated that T cell reactivity and particularly IFN-gamma secretion against Ag 85, but not against ML18 and ML65, might be a predominant mechanism in the early stages of acquired protective immunity against Myco. leprae.