World Health Organization Multidrug Therapy Research Articles

Seventy years of evidence on the efficacy and safety of drugs for treating leprosy: a network meta-analysis

The World Health Organization (WHO) recommends multidrug therapy (MDT) with rifampicin, dapsone, and clofazimine for treating leprosy, which is based on very low-quality evidence. Here, we performed a network meta-analysis (NMA) to produce quantitative evidence to strengthen current WHO recommendations. All studies were obtained from Embase and PubMed from the date of establishment to October 9, 2021. Data were synthesized with frequentist random-effects network meta-analyses. Outcomes were assessed using odds ratios (ORs), 95% confidence intervals (95% CIs), and P score. Sixty controlled clinical trials and 9256 patients were included. MDT was effective (range of OR: 1.06-1255584.25) for treating leprosy and multibacillary leprosy. Six treatments (Range of OR: 1.199-4.50) were more effective than MDT. Clofazimine (P score=0.9141) and dapsone+rifampicin (P score=0.8785) were effective for treating type 2 leprosy reaction. There were no significant differences in the safety of any of the tested drug regimens. The WHO MDT is effective for treating leprosy and multibacillary leprosy, but it may not be effective enough. Pefloxacin and ofloxacin may be good adjunct drugs for increasing MDT efficacy. Clofazimine and dapsone+rifampicin can be used in the treatment of a type 2 leprosy reaction. Single-drug regimens are not efficient enough to treat leprosy, multibacillary leprosy, or a type 2 leprosy reaction. All data generated or analyzed during this study are included in this published article [and its supplementary information files].

The Profile of Type 1 Leprosy Reaction at Leprosy Division of Dermatology and Venerology Outpatient Clinic of Dr. Soetomo General Academic Hospital, Surabaya, Indonesia

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Type 1 leprosy reaction is a delayed hypersensitivity reaction caused by the increased response of cellular-mediated immunity to the Mycobacterium leprae antigen on the skin and nerves with a reversal result. The clinical manifestation includes inflammation which can cause skin and nerve lesions, swell, to permanent disabilities. Purpose: To describe the demographic and clinical profile of type 1 leprosy reaction at the Leprosy Division of the Dermatology and Venerology Outpatient Clinic of Dr. Soetomo General Academic Hospital in 2017–2019. Methods: This was a descriptive study. We used secondary data from the medical records of leprosy patients at the Leprosy Division of Dermatology and Venereology outpatient clinic, Dr. Soetomo General Academic Hospital Surabaya, from January 2017 to December 2019. Result: Out of 364 patients, 65 (17.9%) had type 1 reactions. They were mostly in productive age at 35–55 years old (56.9%). The patients were predominantly male (75.4%), with normal nutritional status (98.5%) and negative bacterial index (72.3%). The most common types of leprosy were BB (Borderline) with 61.6% and BL (Borderline Lepromatous) with 20.8%. All patients took WHO (World Health Organization) MDT (Multi Drug Therapy) MB (Multi-Bacillary). Conclusion: The profile of type 1 leprosy reaction at the Leprosy Division of Dermatology and Venerology Outpatient Clinic of Dr. Soetomo General Academic Hospital in 2017–2019 shows an average data as follows: age 35–55 years, male, normal nutritional status, negative bacterial index, leprosy type BB.

Treatment of multibacillary leprosy following the development of dapsone hypersensitivity syndrome

Background: World Health Organization (WHO) multi-drug therapy (MDT) is the current standard treatment for leprosy. A wide range of frequency of adverse effects caused by MDT has been reported. Dapsone hypersensitivity syndrome (DHS) is a serious adverse effect caused by dapsone. Prompt withdrawal of dapsone is important aspect in the management of DHS. Alternative regimens are needed to treat leprosy patient with DHS. Case Illustration: A 37-year-old man with multibacillary (MB) leprosy developed DHS in 39 days after the initiation of WHO MDT. Dapsone was withdrawn and methylprednisolone of 75 mg/day was prescribed. Twelve days after admission the patient showed clinical and laboratory improvement and was discharged. Treatment for multibacillary leprosy was continued with rifampicin and clofazimine with standard dosage. The bacterial index (BI) and morphological index (MI) showed +1 and 0 respectively in one month after the completion of 12 pulses of modified MB-MDT. Discussion: In the event of severe dapsone toxicity like DHS, WHO recommends that no modification to MDT is required other than immediately stopping dapsone in the case of those receiving MB-MDT. Multiple doses of rifampicin, ofloxacin and minocycline (ROM) therapy can be used as another alternative in leprosy patient with severe adverse effect while taking dapsone. Conclusion: Combination of rifampicin and clofazimine may be effective in treating MB leprosy with dapsone toxicity. Keywords : dapsone, dapsone hypersensitivity syndrome, leprosy, WHO MDT

Alternate Anti-Leprosy Regimen for Multidrug Therapy Refractory Leprosy: A Retrospective Study from a Tertiary Care Center in North India.

A subset of multibacillary (MB) leprosy patients manifest with clinical "nonresponsiveness" to the fixed-duration, World Health Organization multidrug therapy MB regimen (WHO-MDT-MBR). The aim of this retrospective study was to assess the effectiveness and safety of alternate anti-leprosy therapy (ALT) in such patients. This is an analysis of patients' records, registered in the leprosy clinic of our institute over a period of 6 years (2010-2015). The criteria for inadequate response/nonresponsiveness to treatment were as follows: 1) persistent/new lesions after completing ≥ 12 months of WHO-MDT-MBR (isolated reactions were ruled out histopathologically) and 2) persistent positive/increasing value of the morphological index (MI) and a 2 log increase in the bacteriological index (BI) after ≥ 12 months of WHO-MDT-MBR. Such cases were treated with ALT consisting of minocycline, clofazimine, and ofloxacin (24 months). Of 556 patients registered during the study period, 40.3% (224) were slit-skin smear (SSS) positive and 59.7% (332) were SSS negative. Of all, 35 patients (6.3%) satisfied the criteria for clinical nonresponsiveness. Of 224 SSS-positive patients, these 35 patients amounted to 15.6%. The mean BI and MI of these patients after completion of ≥ 12 months of WHO-MDT-MBR were 5.3 ± 0.6 and 14 ± 6.8%, respectively. After 6 months of treatment with ALT, MI became negative (0) in all these patients. After completion of ALT, the mean BI and MI became 1.7 ± 0.7 and 0%, respectively (P < 0.0001). There were 16 patients with corticosteroid-dependent recurrent/chronic erythema nodosum leprosum, who had excellent response with significant reduction in the number of reactional episodes and mean dose of prednisolone required (P < 0.0001). No serious adverse effects were noted. We conclude that ALT is safe and effective in the management of MB leprosy patients who are nonresponsive to 12 months of WHO-MDT-MBR.

Medically Significant Hypersensitivity Reaction to Dapsone: A Case Report

The drug Dapsone is a component of the World Health Organization multidrug therapy being used against leprosy. Although it has shown a good efficacy during the years, a few subjects develop adverse drug reactions associated with dapsone .We report a case of a patient who was prescribed dapsone as part of multiple drug therapy for leprosy following which he developed Dapsone induced Hypersensitivity Syndrome (DHS). He was prescribed steroids with a tapering dose. His condition worsened after weaning of the oral steroids. He also developed steroid-induced diabetes which was stabilized using anti-diabetic drugs.

Histoid leprosy: a retrospective study of 40 cases from India

Rare variants of leprosy pose a diagnostic challenge even to astute clinicians and histoid leprosy is one such form of disease with unique clinical and histopathological features. There are very few large series on this entity, mainly reported from India. To study the epidemiological and clinical characteristics of patients with histoid leprosy. We undertook this retrospective study including patients registered with the leprosy clinic of our tertiary care referral centre from January 1991 to December 2006. Data regarding demographic details, clinical features, treatment, complications and course following treatment were extracted from the records of the leprosy clinic. The incidence of histoid leprosy among the registered patients of our clinic was 1.8% (40 of 2150). There was a significant male preponderance with a male/female ratio of 5.7 : 1. The anatomical areas of involvement were thighs/buttocks (67.5%), arms (62.5%), back (52.5%), face (47.5%), forearms (47.5%) and legs (35%) in descending order of frequency. This variety of leprosy was found most commonly in patients with a primary diagnosis of lepromatous leprosy (40%). De novo histoid lesions, i.e. lesions of histoid leprosy developing without evidence of lesions of other types of leprosy in the Ridley-Jopling classification, appeared in 12.5% of patients only. Only three patients had received antileprosy treatment before presentation. Episodes of erythema nodosum leprosum (ENL) had occurred in 40% of patients, although only one patient manifested ENL after the diagnosis of histoid leprosy. The disease responded satisfactorily to the respective World Health Organization multidrug therapy regimens in all except in one patient who relapsed with borderline lepromatous leprosy. As the bacillary load is very high in these patients, they can form a potential reservoir of the infection in the community especially in the postleprosy elimination era. Contrary to the earlier belief in the dapsone era, most of our patients manifested disease without any history of inadequate or incomplete antileprosy therapy.

Noncompliance with the World Health Organization-Multidrug Therapy Among Leprosy Patients in Cebu, Philippines: Its Causes and Implications on the Leprosy Control Program

The success of current World Health Organization (WHO) key strategy for leprosy elimination (ie, multidrug therapy [MDT] regimen) depends largely on the efficiency of health care delivery services and patient compliance. A high rate of noncompliance with this regimen has serious implications for the leprosy control program because it can set the stage for the emergence of drug resistance, eventually resulting in treatment failure and failure of the program. A community-based descriptive study using pretested interviews conducted in 12 leprosy endemic areas in Cebu, Philippines, showed that the noncompliance rate with the WHO-MDT regimen among 233 study subjects was 30%. The causes of noncompliance are drug-related, health care provider-triggered, or patient-inducted, or some combination of these. Recommendations on strategic interventions to obviate the cause for noncompliance are presented.

PARALLEL ASSESSMENT OF 24 MONTHLY DOSES OF RIFAMPIN, OFLOXACIN, AND MINOCYCLINE VERSUS TWO YEARS OF WORLD HEALTH ORGANIZATION MULTI-DRUG THERAPY FOR MULTI-BACILLARY LEPROSY

Monthly doses of rifampin, ofloxacin, and minocycline (ROM) are expected to be effective treatment for multi-bacillary leprosy. Patients with MB leprosy received ROM (n = 10) or World Health Organization multi-drug therapy (MDT) (n = 11). Treatment with ROM was given as 24 consecutive monthly observed doses of rifampin (600 mg), ofloxacin (400 mg), and minocycline (100 mg). Treatment with MDT was given as 24 consecutive monthly observed doses of rifampin (600 mg) and clofazimine (300 mg), and unobserved daily dapsone (100 mg) and clofazimine (50 mg). Twenty patients completed the 24-month regimens with > 99% compliance. Treatments with ROM and MDT were safe, tolerable, and caused similar improvements in lesions, bacterial indices, and histology. All MDT recipients developed clofazimine-induced pigmentation. Six ROM and nine MDT recipients assessed at five or more years after completion of treatment had no evidence of relapse. Twenty-four months of treatment with ROM is a safe, well-tolerated, and convenient regimen that may provide an alternate therapy to MDT for MB leprosy. Larger trials with sufficient follow-up would better define the role of ROM.

A Comparative Study Between 12 and 24-Dose Therapeutic Regimens for Multibacillary Leprosy Patients

A comparative study was made of the initial and final bacterial indices (BIs) of 213 MB leprosy patients who had been administered 12-dose (Group 1/128 patients) and 24-dose (Group 2/85 patients) World Health Organization multi-drug therapy to measure the effectiveness of both treatment regimens. All patients were evaluated at the beginning of treatment, at 12 months, and again after 24 months had elapsed. Decline in BI values and average BIs at 24 months were found to be similar for both groups. Moreover, no statistical difference between the two treatment regimens was found in the frequency rate of reaction.

Current World Health Organization-sponsored studies in the chemotherapy of leprosy

Until the early 1 980s, dapsone monotherapy administered to known patients was used for control of leprosy. Dapsone was usually administered in a dosage of 100 mg daily for a minimum of 5 years to patients with paucibacillary (PB) leprosy, and for life to patients with multibacillary (MB) leprosy. Because it was a weakly bactericidal and slowly acting drug, dapsone monotherapy led to poor patient compliance and the emergence of dapsone-resistant strains of Mycobacterium leprae. Since 1982, the multidrug therapy (MDT) regimens recommended by the World Health Organization (WHO), which include a combination of rifampicin, clofazimine and dapsone for MB leprosy and rifampicin plus dapsone for PB leprosy, have been applied in national leprosy control programmes in all of the leprosy endemic countries in the world. This therapy has proved to be a most reliable and practical method of treating leprosy. The introduction of MDT in 1982 has resulted in a dramatic reduction of the prevalence of leprosy, from 5 ·4 million registered cases in 1 985 to 0·8 million in 1999. By the end of 1999, more than 10 million patients had been cured by MDT. Follow-up of the large number of patients cured by MDT has revealed very low relapse rates after stopping treatment; the cumulative risk of relapse is less than 1 % over a period of 9 years for both MB and PB leprosy. Despite the success of the standard WHO MDT regimens, there is a need for more effective combined drug regimens. Several WHO-sponsored programmes of research in the chemotherapy of leprosy are currently in progress. The purpose of this report is briefly to describe the programmes and their current status.

Experimental evaluation of possible new short-term drug regimens for treatment of multibacillary leprosy.

Groups of nude mice, with both hind footpads infected with 10(8) Mycobacterium leprae organisms, were treated with 4-week courses of different drug combinations. The effect treatment on each group was evaluated by subinoculating footpad homogenates from the treated mice into groups of normal and nude mice for subsequent regrowth, assessed 1 year later. A combination of rifampin (RMP) with clarithromycin (CLARI), minocycline (MINO), and ofloxacin (OFLO) resulted in the complete killing of M. leprae after 3 weeks of treatment. A combination of sparfloxacin (SPAR) and RMP also resulted in a similar bactericidal effect after 3 weeks of treatment. Other drug combinations showed variable effects. Very little or no effect was observed with any regimen if the treatment was given for less than 2 weeks. World Health Organization (WHO) multidrug therapy (MDT) given for 8 weeks was as effective as the two combinations described above. The results suggest that multidrug combinations consisting of RMP-OFLO (or SPAR)-CLARI (and/or MINO) are as effective as the WHO MDT for the treatment of experimental leprosy. Moreover, they imply that these combinations, which were found to be active in a 4-week experimental treatment protocol, could be administered as treatment to patients for a period of time shorter than the present 2-year regimen without a loss of effectiveness.