Study of 39 documented relapses of multibacillary leprosy after treatment with rifampin

Among 39 strains of Mycobacterium leprae isolated from patients with multibacillary leprosy who relapsed after treatment with rifampin (RMP), 22 strains were resistant to RMP and 17 were susceptible. All of the RMP-resistant strains were recovered from patients who had been treated with more than 50 doses of RMP, usually given as monotherapy. RMP-susceptible strains were recovered from only six patients who had received more than 50 doses of RMP, and from 11 patients who had received no more than seven doses. The median time to relapse after the beginning of RMP therapy was 9 years (range 1-12 years) among the patients harboring RMP-resistant strains of M. leprae, and the median time to relapse after discontinuation of RMP treatment was 7 years (range 1-11 years) among the patients harboring RMP-susceptible strains. These data suggest that monotherapy with more than a few doses of RMP can be responsible for the emergence of RMP-resistant strains of M. leprae, thus emphasizing the need to employ RMP only in combination with other effective drugs in the chemotherapy of multibacillary leprosy.     

Progression of acral bone resorption in multibacillary leprosy

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.     

Composite skin contact smears in multibacillary leprosy patients

"Composite skin contact smears" technique was used in 20 multibacillary leprosy patients to find out the presence of AFB on their intact skin. One hundred and twenty one AFB were found in 930 sq.cm. area of skin surface examined. Seventy-five AFB were solidly staining and 46 were granular. The bacilli were found in all the sites examined. Immunofluorescent staining showed M. leprae in one out of four patients. The number of bacilli discharged from the intact skin seems adequate for the transmission of leprosy considering the large surface area of the skin and evidence in mouse experiments that multiplication of M. leprae can be obtained after inoculation of very small number of bacilli.     

Ovarian function in female patients with multibacillary leprosy

Eighty six adult female patients with multibacillary leprosy were included to study the sex hormone profile LH, FSH, and prolactin, as well as their gynecological events like menstrual function and fertility status. A third of the patients gave a history of irregularity of periods. The mean levels of LH and FSH were significantly higher in patients with multibacilary leprosy vis-à-vis the controls. Of the 24 married women with irregularity of periods, 12 (50%) were infertile. Seven of these patients had elevated levels of FSH and LH, almost reaching castration levels.     

"Nose-blow" smears in multibacillary leprosy patients

332 nose-blow specimens have been examined from 73 untreated multibacillary patients of leprosy before and periodically after they were put on a maximal, minimal or an intermediate multi-drug regimen. 80% of these specimens were found to be positive for acid fast bacilli initially. Bacillary positivity rate was more in samples containing pus or blood. Bacilli were seen in LL, LI as well as BL patients. Nearly half of the cases became negative for AFB in their nose-blow specimens within 3 months of initiation of treatment whereas none of these patients has become negative in skin smears. However, a few cases have continued to discharge bacilli in their nasal secretions even after 12 months of multi-drug regimen therapy.     

Multidrug therapy in multibacillary leprosy; experience in an urban leprosy center.

The article records the experience of treating multibacillary (BB, BL and LL) leprosy with multidrug therapy (MDT) in an urban leprosy center. The problem of leprosy is to be properly assessed throughout the Indian subcontinent because most of the epidemiological data from the areas labeled low-endemic have to be updated. The regularity of therapy must be ensured and monitored constantly, but in spite of our efforts to do so some factors were beyond our control, such as providing a means of livelihood for the migrants from other places. In addition, the intake of drugs also has to be periodically checked from the history and discoloration of skin and, most importantly, confirmed by performing random spot tests for dapsone in the urine. The main problems discussed are the difficulty in demonstrating acid-fast bacilli in slit-skin smears from the macular form of borderline leprosy (also called dimorphous macular) and, secondly, whether the duration of multibacillary therapy was adequate since only approximately 50% of our patients achieved smear negativity after taking MDT for the stipulated period of 24 months. Experiences from other centers have suggested that the duration of MDT should be prolonged in multibacillary patients to achieve smear-negative status. Yet another group notes that smear negativity is gradually achieved during the period of surveillance following stoppage of MDT after 24 months. These questions await more information from good centers with controlled field studies.     

Risk of paucibacillary leprosy patients released from control relapsing with multibacillary leprosy

We studied 51 paucibacillary patients who had relapsed after cessation of dapsone monotherapy. Among the 51 relapses, the lepromin-negative group had a significantly higher risk of relapsing with multibacillary leprosy compared with the lepromin-positive group of patients. The significance of these findings is discussed.     

Immunochemotherapy with interferon-gamma and multidrug therapy for multibacillary leprosy

Treatment for multibacillary leprosy is presently performed with a multidrug therapy (MDT) scheme maintained for 2 years. Leprosy treatment however can benefit from the reduction of length. The lack of interferon-gamma (IFN-gamma) production by lepromatous leprosy (LL) patients' lymphocytes lead us to use this cytokine in the treatment of multibacillary leprosy associated with MDT in the treatment of multibacillary leprosy, and monitor several clinical and immunological parameters during the course of treatment. A total of 20 multibacillary leprosy patients were evaluated, 10 treated with MDT alone, and 10 treated with MDT + 10 daily doses of 2 x 10(6) international units (IU) of recombinant human IFN-gamma/m2 followed by 10 daily doses of 10(7) IU IFN-gamma/m2, intramuscularly, during the first 20 days of MDT. IFN-gamma was well tolerated and did not cause any increase in the rate of leprosy reactions development during treatment. Decrease of bacillary load, fall of anti-Mycobacterium leprae IgG serum antibodies, changes of histological pattern, as well as changes in lymphocyte proliferation assay in response to mitogens (PHA or PWM), M. leprae antigen or PPD was similar in both groups of patients. Among several soluble immunological markers measured before and 30 days after beginning of treatment, levels of soluble IL-2R receptor increased in patients treated with MDT plus IFN-gamma whereas decreased in patients treated with MDT alone. Soluble ICAM-1 levels decreased in the MDT group but did not change in the MDT + IFN-gamma treated patients. Soluble CD4 and soluble CD8 markers did not change significantly in either group of patients. Neopterin, a marker of macrophage activation, increased in all but one patient treated with MDT + IFN-gamma but in none treated with MDT alone, indicating that IFN-gamma was active in vivo. Our findings indicate that despite being able to promote macrophage activation in multibacillary leprosy patients a short course of systemically administered IFN-gamma is not able to change the clinical course of a long standing disease such as leprosy.     

Pattern of bacillary clearance in multibacillary leprosy patients with multidrug therapy

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.     

Immunomodulator treatment of multibacillary leprosy using extracts of microbial ribosomes

Ribomunyl can in practice be profitably included in the range of immunostimulants, but it requires weekly injections and hence surveillance that will also enable any adverse reactions to be monitored. Its action and tolerance after polychemotherapy have still to be studied. On the basis of our experience, we feel that only isoprinosine, whose effectiveness and good tolerance we have demonstrated, can be used for self-treatment in a mass campaign.     

Studies on risk of leprosy relapses in China: relapses after treatment with multidrug therapy

Based upon the data from the Chinese National System for Leprosy Surveillance, this paper reports on the relapses in 47,276 leprosy patients cured by or released from WHO-recommended multidrug therapy (WHO/MDT). The overall relapse rate was 0.73/1000 patient-years (PY). There was a statistically significant difference in the relapse rates of WHO/MDT-MB (0.61/1000 PY) and WHO/MDT-PB (1.04/1000 PY) (chi 2 = 15.7, p < 0.01) patients. For multibacillary (MB) patients, the relapse rate in patients treated with fixed-duration MDT (0.56/1000 PY) was comparable with that in patients treated with MDT until skin-smear negativity (0.73/1000 PY) (chi 2 = 2.20, p > 0.05). Our present study suggests that fixed-duration MDT is a cost-effective regimen for the treatment of leprosy in China. The present results also show that relapse of leprosy is acceptably low and has not yet become a serious clinical or public health problem but, based upon the incubation of relapse in MDT patients, it is necessary to encourage annual follow up for at least 5 years for paucibacillary (PB) and 10 years for MB patients after being released from WHO/MDT.     

Studies on risk of leprosy relapses in China: relapses after treatment with dapsone monotherapy

Based upon the data from the Chinese National System for Leprosy Surveillance, this paper reports on the relapses in 297,343 leprosy patients [multibacillary (MB) 106,518, paucibacillary (PB) 190,825] cured by dapsone monotherapy. A total of 11,055 (MB 8675, PB 2380) patients relapsed during an accumulated follow-up period of 4,229,050 patient-years (PY), giving an overall relapse rate of 3.72 per 100 cases or 2.61 per 1000 PY, i.e., 8.14% or 5.91 per 1000 PY over an average follow-up period of 13.8 +/- 8.4 years in MB patients and 1.25% or 0.86 per 1000 PY over an average period of 14.5 +/- 8.9 years in PB patients. For either the overall relapse rate per 100 cases or per 1000 PY, the differences between MB and PB patients were statistically significant, except during 36-40 years of follow up. For both MB and PB patients, the relapse rates showed consistently significant decreases year by year, particularly in PB patients whose relapse rate per 1000 PY was 1.21 in year 10 of follow up; whereas it remained more than 10 per 1000 PY in MB patients. In view of that, the overall relapse rates in MB and PB patients cured by dapsone monotherapy were acceptably low, and most of these patients have been followed up for more than a mean incubation period of observed dapsone relapse. Along with the further extension of follow up, the risk of relapse in dapsone-cured patients will not be expected to increase. This conclusion should be considered when planning policy for the management of patients released from dapsone monotherapy.     

Hepatotoxicity of the combination of rifampin-ethionamide in the treatment of multibacillary leprosy

During treatment of multibacillary leprosy with the combination rifampin (RMP) 600 mg, ethionamide (ETH) 500 mg, and either dapsone (DDS) or clofazimine (CLO) 100 mg, hepatotoxicity was observed in 4.5% of 596 patients. Hepatitis appeared after 5-186 days, with a mean of 93 days and a median of 76 days. Mortality was 26%. ETH and DDS or CLO were administered daily in all regimens in which hepatitis occurred. RMP was given either daily or daily during the first two weeks or eight weeks, followed by a once-weekly dose. It is concluded that the combination RMP + ETH is the toxic component. In some patient groups there was a high correlation of toxicity with age. A regimen in which RMP was administered only twice a week during three months was not accompanied by hepatotoxicity. Future studies should show if reduction of the daily dose of ETH or reduction of the duration of the administration of RMP + ETH might reduce the incidence of hepatotoxicity while conserving the efficacy.     

Indeterminate leprosy: histopathologic and histochemical predictive parameters involved in its possible change to paucibacillary or multibacillary leprosy

In an attempt to find clinical, bacteriological, histopathological, and immunohistochemical parameters to predict the progress of indeterminate leprosy patients to either paucibacillary (PB) or multibacillary (MB) leprosy, skin biopsies from 51 patients with indeterminate leprosy were retrieved from the files of the S?o Paulo Health Institute (Brazil). All of these patients had progressed to either PB or MB leprosy over a period of time which varied from 2 months to 24 years. Clinical records were examined, and new sections were cut from the paraffin blocks and stained by hematoxylin-eosin and Fite-Faraco stains; the avidin-biotin peroxidase technique was used with primary antibodies to detect bacillary antigens (anti-BCG serum) and nerve branches (anti-S-100 protein anti-serum). A moderate (++) or strongly positive ( ) Mitsuda skin test was observed in some patients progressing to PB leprosy. Noteworthy is that even patients initially Mitsuda negative may evolve to PB leprosy. a) A 2+ bacterial index and/or the presence of bacilli, even though few in number, in various dermal structures; b) multiple positive antigen sites as detected by anti-BCG anti-serum; and c) dermal nerve involvement, when evaluated as single parameters, correlated with a progression indeterminate to MB leprosy. An index resulting from the summation of the above three parameters identified 13 (72%) of 18 of these cases which progressed to MB leprosy.     

Efficacy of combined treatments comprising 6 months' administration of rifampicin in multibacillary leprosy

Ten patients infected with mouse proven DDS-resistant bacilli were treated with the following combined regimen: RMP 600 2/7 6 months, ETH 500 7/7 6 months and DDS 100 7/7 12 months. Follow up was for 27-54 months, without relapses. Added to patients from previous study (Int. J. Lepr. 1984, 52, 297-303) the 95% confidence limit decreases from 12 to 9%.     

Relapses vs. reactions in multibacillary leprosy: proposal of new relapse criteria

Objectives To compare a new scoring system for multibacillary (MB) leprosy relapses, which combines time factor, risk factors and clinical presentation at relapse, to WHO criteria. Methods Data were collected on all relapses diagnosed between 1998 and 2004 at the Marie‐Adelaide‐Centre in Karachi, Pakistan, including case histories, clinical manifestations, follow‐up, bacterial indices, treatment and contacts. For the diagnosis of MB relapses a simple scoring system was developed and validated on a data‐set of mouse foot pads (MFP)‐confirmed relapses (Leprosy Reviews, 76 , 2005, 241). Its sensitivity was further evaluated in the Karachi relapse cohort. The P‐value was calculated with McNemar’s test with continuity correction. Results The new scoring system that combines time factor, risk factors and clinical presentation at relapse had a higher sensitivity in MFP‐confirmed relapses than the WHO‐criteria (95%vs. 65%, P < 0.01). The sensitivity of the scoring system was also significantly higher than the WHO criteria in the 57 cases of MB‐relapses diagnosed in Karachi (72%vs. 54%, P < 0.05). Conclusions This new simple scoring system for diagnosing MB‐relapses in leprosy should be further validated in a prospective study to confirm its superior sensitivity and to evaluate the specificity of these criteria by using MFP‐confirmation for patients presenting with signs of activity after treatment.