Multidrug Therapy For Leprosy Research Articles

Causality, severity, and preventability of adverse drug reactions due to multi-drug therapy in leprosy: evidence from a national level institution in Sri Lanka

Objective This study describes the causality, severity, and preventability of adverse drug reactions (ADR) in patients affected by leprosy treated with multi-drug therapy (MDT) at the dermatology and central leprosy clinics of the National Hospital of Sri Lanka. Methods This cross-sectional analytical study consisted of two components (retrospective and prospective). Prospective cases were recruited and followed up for six months. Retrospective data collection was carried out at relevant clinics in the NHSL by extracting data from the clinical records of the patients. When an ADR was suspected, it was confirmed after discussion with the clinic medical officers/consultant dermatologist and scored according to the Naranjo ADR probability scale. The intensity of an individual ADR was evaluated using the modified Hartwig and Siegel Severity Assessment Scale, and preventability assessment was performed using the modified Schumock and Thornton scale. Results One hundred and ninety-seven patients were included for ADR attributable to MDT. Approximately 145 patients (73.6%) developed ADR associated with dapsone. Another 50 cases (25.3%) were associated with rifampicin, and 10 (5.1%) were associated with clofazimine. Of the dapsone related 145 ADRs, 59 (40.7%) were definite, 64 (44.1%) were probable, and 22 (15.2%) were possible. Of the rifampicin-related cases, four (8%) were definite, 35 (70%) were probable, and 11 (22%) were possible. The most common adverse drug reactions detected were haemolytic anaemia and hepatic abnormalities due to MDT. Dapsone was discontinued in 40% (59 out of 145) of these patients, while rifampicin was stopped in 8% (4 out of 50) of patients. Clofazimine was not stopped in any of the patients. Conclusions Adverse drug reactions associated with multidrug therapy in leprosy are common among patients diagnosed with leprosy in Sri Lanka. Most ADRs reported in this study were of mild severity and preventable. Careful monitoring and objective scales are needed to identify ADRs at an early stage.

CHALLENGES IN MANAGEMENT OF BORDERLINE LEPROMATOUS LEPROSY COMPLICATED BY DAPSONE INDUCED HEMOLYTIC ANEMIA AND LEPRA REACTION: A CASE REPORT.

Multidrug therapy for Leprosy is currently done with Dapsone, Clofazimine and Rifampicin. Dapsone is known to cause hemolytic anemia and this adverse event during MDT seems to be more frequent than reported. Lepra reactions can occur at presentation, during treatment or even after completion of MDT. Inadequate and interruption of treatment is an obstacle to eradication. 65 year old female clinically diagnosed leprosy, as patient developed multiple hypopigmented plaques on skin and swelling and decreased sensation over right hand initiated on MDT presented with complains of hematuria on Day 4 of therapy. Blood investigation revealed hemolytic anemia. Dapsone was stopped and blood products given. Dapsone inhibits bacterial synthesis of Dihydrofolic acid. The main side-effects usually described are allergic, such as itchy rash and exfoliative dermatitis, hemolytic anemia (HA), jaundice, methemoglobinemia and dapsone syndrome. Type 1 reaction or “reversal reaction" presents with worsening of pre-existing skin lesions, thickening of nerve ber with neuropathy and edema. Type 2 reaction or erythema nodosum leprosum (ENL) have painful erythematous skin nodules. This case highlights fundamental understanding of the treatment options, prompt diagnosis and treatment of reactions which are essential to reduce disease burden and improve patient's quality of life.

Interaction between leprosy and HIV infection

Introduction: Leprosy and Human Immunodeficiency Virus (HIV) infections still count as major health issues worldwide. Starting with the HIV pandemic back in the eighties, leprosy was feared to re-emerge as the HIV cases arose. Co-infections between leprosy and HIV were worried to cause an increase in leprosy cases, with worse clinical manifestation, predominantly toward the lepromatous spectrum, decrease in therapy response, and prolonged therapy period. Unlike its interaction with tuberculosis, HIV infection was turned out to not increasing nor deteriorating the manifestation of leprosy infection. All clinical spectrum of leprosy was found in HIV infection patients without predomination of lepromatous type. Responses to leprosy Multi-Drug Therapy (MDT) regimen were also found similar between leprosy patients with or without HIV.
 Conclusion: It is recommended to treat co-infective patients both with leprosy MDT and antiretroviral therapy. Manifestation of leprosy as a part of immune reconstitution syndrome need more attention and investigation.

Utility of a Mycobacterium leprae molecular viability assay for clinical leprosy: An analysis of cases from the Philippines, Ethiopia, and Nepal

Mycobacterium leprae is a slow-growing species of mycobacteria that cannot be cultured in axenic media. This presents a number of challenges for monitoring treatment efficacy and advancing new drugs and regimens for treating leprosy. We previously developed a molecular viability assay (MVA) which measures expression of hsp18 and esxA transcripts to determine viability of M. leprae directly from infected tissue. The objective of the current study was to determine the utility of the MVA for practical use on clinical specimens. Leprosy cases from the Philippines (N = 199), Ethiopia (N = 40), and Nepal (N = 200) were diagnosed by clinical examination, slit-skin smears (SSS) from index sites, and/or histopathology. Biopsy specimens for MVA were collected from an active lesion and stored in 70% ethanol. DNA and RNA were extracted from the tissue, and M. leprae were enumerated on the DNA fraction via RLEP qPCR. Based on this count, DNased RNA was normalized to the equivalent of 3x103M. leprae per reverse transcription reaction, and hsp18 and esxA transcripts were amplified by PCR on the resulting cDNA. There was a strong correlation between RLEP enumeration on the specific biopsy specimen for MVA and the average SSS bacterial index (BI) in all three cohorts (p < 0.001). The MVA could be performed on most biopsies with an average SSS BI ≥ 2 and showed a decrease in M. leprae viability with increasing duration of leprosy multidrug therapy (R2 = 0.81, p < 0.001). The MVA also detected viable M. leprae in relapse patients where it showed significant correlation with the mouse footpad assay (p = 0.018). The MVA is a M. leprae-specific, sensitive, and relatively quick test. Clinically, the MVA would likely be most useful to monitor treatment, confirm suspected relapse cases, and determine efficacy of new leprosy drugs in clinical trials.

Appraisal of Inter-rater Agreement among Assessment Scales and Retrospective Analysis of Validated Reports of Cutaneous Adverse Drug Reactions at Tertiary Care Hospital in Eastern India

Introduction: Cutaneous Adverse Drug Reactions (CADRs) share significantly to Adverse Drug Reactions (ADRs) comprising 10%-30% of all ADR reporting in India. Multi Drug Therapy for Leprosy (MDT-L) and antimicrobials contribute remarkably to the overall CADRs burden. Aim: To show distinctive pictures of CADRs profile and to assess inter-rater agreement of assessment scales among study populations. Materials and Methods: A retrospective analysis was done for 245 CADRs reported from March 2018 to March 2020. Cohen kappa statistics was applied for inter-rater agreement study for causality (World Health Organisation-Uppsala Monitoring Cente {WHO-UMC} Scale and Naranjo’s Algorithm), severity (Hartwig and Siegel scale) and preventability assessment (Modified Schumock and Thornton scale). Results: CADRs contribute 45.54% of total ADRs reported during study period. Male (60.41%) and age group 21-40 years (22.45%) were predominant sex and age group, respectively. Multidrug therapy for leprosy (51.83%) was the most common offending agent and hyperpigmentation (20.82%), dryness (13.1%), and both (11%) were the most prevalent CADRs. Causality of WHO–UMC Scale was higher with ‘Possible’ than ‘Probable’. Whereas, ‘Probable’ was maximally found with Naranjo’s Algorithm. Severity assessment showed maximum ‘mild’ cases i.e., 66.53% (manual) and 69.8%% (app). Preventability assessment depicted mostly ‘Definite’, 66.53% (manual) and 85.71% (app). Inter-rater agreement study showed ‘Substantial agreement’ for WHO-UMC Scale (K=0.678) and Naranjo’s algorithm (K=0.820), when manual vs app ratings were compared. ‘Almost perfect’ for severity assessment (K=0.893) and ‘Moderate’ for preventability assessment (K=0.434) were noticed. ‘Fair’ agreement was observed when manual (WHO-UMC scale) vs manual (Naranjo’s algorithm) were compared with K=0.290 and also, in app (WHO-UMC scale) vs app (Naranjo’s algorithm) with K=0.319. Conclusion: CADRs were most prevalent among ADRs which have a distinctive picture in eastern India. WHO- UMC scale and Naranjo’s algorithm concluded significant differences in causality with only ‘fair’ agreement between them. Severity and preventability assessment done by manually little varied in their results with pharmvigill app and is still more reliable and popular.

The adverse drug effects of dapsone therapy in leprosy: a systematic review

Objectives: To establish the rate of adverse drug reactions (ADR) when dapsone is given in leprosy multi-drug therapy (MDT). This paper reviews the reporting of ADRs by systematic review of the databases Ovid Medline, Ovid Embase and Global Health according to pre-specified eligibility criteria. Results: The search identified 5859 relevant citations. These publications were divided into two data sets and reviewed for their documentation of ADRs. One hundred and fourteen publications reported ADR as the primary outcome and 98 papers reported the efficacy of treatment. Of the 114 papers included, 79 were case reports, 23 retrospective studies, 7 prospective studies and 7 literature reviews. Dapsone Hypersensitivity Syndrome (DHS) was reported most frequently as an adverse effect, then anaemia (haemolytic and not otherwise specified), cutaneous eruptions, gastrointestinal disturbance and hepatitis. Eleven studies report a mean rate of DHS as 1.22% and an average fatality rate in 8 studies of 11.24%. Of the 98 papers reporting treatment efficacy, 33 papers reported ADRs to medications other than dapsone and 36 publications had no documentation of adverse effects. Conclusion: Most publications report ADRs in case reports, many from India. DHS was the most commonly reported ADR, followed by individual features of the syndrome. Many studies lack patient information with many not reporting ADRs. Our findings show that improved prospective monitoring of adverse events associated with dapsone is needed. We propose that all patients should be tested with a full blood count before starting MDT and repeated after 4–8 weeks with mandatory follow-up. This would facilitate detecting ADRs including DHS and dapsone-associated anaemias.

Hypovitaminosis D and reduced cathelicidin are strongly correlated during the multidrug therapy against leprosy

Mycobacterium leprae infection depends on the competence of the host immune defense to induce effective protection against this intracellular pathogen. The present study investigated the serum levels of vitamin D and the antimicrobial peptide cathelicidin, to determine the statistical correlation between them in leprosy patients before and post-six months of multidrug therapy (MDT), household contacts, and healthy individuals. Previous studies associated these molecules with high risks to develop mycobacterial diseases, such as tuberculosis and leprosy. A total of 34 leprosy patients [paucibacillary (n = 14), multibacillary (n = 20)], and 25 household contacts were recruited. Eighteen healthy adults were selected as a control group. Serum concentrations of vitamin D (25(OH)VD3) and cathelicidin were measured using high-performance liquid chromatography (HPLC), and an enzyme-linked immunosorbent assay (ELISA) kit, respectively. There were no significant differences in serum levels of 25(OH)VD3 between all groups, and the overall prevalence rate of vitamin D deficiency was 67.1%. Cathelicidin levels were significantly lower in both untreated and treated patients when compared to controls and household contacts (p < 0.05). Strong correlations between hypovitaminosis D and reduced cathelicidin in untreated (r = 0.86) and post-six months of MDT (r = 0.79) leprosy patients were observed. These results suggest that vitamin D status and cathelicidin levels are strongly correlated during multidrug therapy for leprosy and nutritional supplementation from the beginning of treatment could strengthen the immune response against leprosy.

Effect of a conditional cash transfer programme on leprosy treatment adherence and cure in patients from the nationwide 100 Million Brazilian Cohort: a quasi-experimental study

SummaryBackgroundIndirect financial costs and barriers to health-care access might contribute to leprosy treatment non-adherence. We estimated the association of the Brazilian conditional cash transfer programme, the Programa Bolsa Família (PBF), on leprosy treatment adherence and cure in patients in Brazil.MethodsIn this quasi-experimental study, we linked baseline demographic and socioeconomic information for individuals who entered the 100 Million Brazilian Cohort between Jan 1, 2007, and Dec 31, 2014, with the PBF payroll database and the Information System for Notifiable Diseases, which includes nationwide leprosy registries. Individuals were eligible for inclusion if they had a household member older than 15 years and had not received PBF aid or been diagnosed with leprosy before entering the 100 Million Brazilian Cohort; they were excluded if they were partial receivers of PBF benefits, had missing data, or had a monthly per-capita income greater than BRL200 (US$50). Individuals who were PBF beneficiaries before leprosy diagnosis were matched to those who were not beneficiaries through propensity-score matching (1:1) with replacement on the basis of baseline covariates, including sex, age, race or ethnicity, education, work, income, place of residence, and household characteristics. We used logistic regression to assess the average treatment effect on the treated of receipt of PBF benefits on leprosy treatment adherence (six or more multidrug therapy doses for paucibacillary cases or 12 or more doses for multibacillary cases) and cure in individuals of all ages. We stratified our analysis according to operational disease classification (paucibacillary or multibacillary). We also did a subgroup analysis of paediatric leprosy restricted to children aged up to 15 years.FindingsWe included 11 456 new leprosy cases, of whom 8750 (76·3%) had received PBF before diagnosis and 2706 (23·6%) had not. Overall, 9508 (83·0%) patients adhered to treatment and 10 077 (88·0%) were cured. After propensity score matching, receiving PBF before diagnosis was associated with adherence to treatment (OR 1·22, 95% CI 1·01–1·48) and cure (1·26, 1·01–1·58). PBF receipt did not significantly improve treatment adherence (1·37, 0·98–1·91) or cure (1·12, 0·75–1·67) in patients with paucibacillary leprosy. For patients with multibacillary disease, PBF beneficiaries had better treatment adherence (1·37, 1·08–1·74) and cure (1·43, 1·09–1·90) than non-beneficiaries. In the propensity score-matched analysis in 2654 children younger than 15 years with leprosy, PBF exposure was not associated with leprosy treatment adherence (1·55, 0·89–2·68) or cure (1·57, 0·83–2·97).InterpretationOur results suggest that being a beneficiary of the PBF, which facilitates cash transfers and improved access to health care, is associated with greater leprosy multidrug therapy adherence and cure in multibacillary cases. These results are especially relevant for patients with multibacillary disease, who are treated for a longer period and have lower cure rates than those with paucibacillary disease.FundingCONFAP/ESRC/MRC/BBSRC/CNPq/FAPDF–Doenças Negligenciadas, the UK Medical Research Council, the Wellcome Trust, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brazil (CAPES).

Interaction between leprosy and HIV infection

Introduction: Leprosy and Human Immunodeficiency Virus (HIV) infections still count as major health issues worldwide. Starting with the HIV pandemic back in the eighties, leprosy was feared to re-emerge as the HIV cases arose. Co-infections between leprosy and HIV were worried to cause an increase in leprosy cases, with worse clinical manifestation, predominantly toward the lepromatous spectrum, decrease in therapy response, and prolonged therapy period. Unlike its interaction with tuberculosis, HIV infection was turned out to not increasing nor deteriorating the manifestation of leprosy infection. All clinical spectrum of leprosy was found in HIV infection patients without predomination of lepromatous type. Responses to leprosy Multi-Drug Therapy (MDT) regimen were also found similar between leprosy patients with or without HIV.Conclusion: It is recommended to treat co-infective patients both with leprosy MDT and antiretroviral therapy. Manifestation of leprosy as a part of immune reconstitution syndrome need more attention and investigation.Keywords: HIV infection, leprosy, interaction

A 19-Year Retrospective Study of Adverse Drug Reactions to Multidrug Therapy in Leprosy Requiring a Change in Regime.

Background and Aims:Multidrug therapy (MDT) in leprosy has brought the prevalence of leprosy to elimination levels. However, these drugs are not without toxicity. The primary aim of this study was to find the prevalence of adverse drug reactions (ADR) to MDT and the secondary aim to study the clinical features of these drug reactions.Materials and Methods:This is a19-year retrospective descriptive study of all new leprosy cases with ADR to MDT, requiring a change in regime.Results:There were 901 new leprosy cases in the study period. There were 28 cases of documented ADR to MDT necessitating a change in regime, thus accounting for a prevalence of 3.11%. There were 24 males (85.71%) and 4 females (14.29%) with a male/female ratio 6:1. Mean age was 39.58 years. Borderline tuberculoid was the commonest type of leprosy in which ADR were seen (46.43%). Dapsone was the commonest drug to cause ADR seen in 17 cases (60.71%). Hepatic involvement in the form of drug-induced hepatitis was the commonest presentation of ADR in this study accounting for 13 cases (46.43%), followed by skin rash, 9 cases (32.14%). There were no ADR reported to clofazimine. No ADR was reported to the alternative regimes given.Conclusions:The prevalence of ADRs was low in this study, with dapsone being the commonest drug. There were no adverse reactions to clofazimine. No adverse reactions were reported with the alternative regimes of ofloxacin and minocycline.

Amino Acid Variants of HLA-DRB1 Confer Susceptibility to Dapsone Hypersensitivity Syndrome in Addition to HLA-B*13:01

Dapsone hypersensitivity syndrome is a rare yet severe adverse drug reaction caused by dapsone, a principal drug in multidrug therapy for leprosy. HLA-B*13:01 has been identified as a strong risk factor of dapsone hypersensitivity syndrome; however, its low positive predictive value indicated that additional genetic variants may be involved in the disease development. To discover contributing genetic variants within HLA loci in addition to HLA-B*13:01, we performed a high-coverage next-generation sequencing (NGS)-based HLA typing analysis in 103 dapsone-hypersensitive and 857 dapsone-tolerant HLA-B*13:01-positive leprosy patients in a Chinese population. Five amino acid variants in high linkage disequilibrium of HLA-DRB1 were significantly associated with dapsone hypersensitivity syndrome (positions 133, 142, -17, 11, and 13). DRB1*16:02 and DRB1*15:01 tagged by these risk-conferring amino acid residues were associated at a nominal significance level. This study identifies five amino acid variants within HLA-DRB1 that are in high linkage disequilibrium and significantly associated with dapsone hypersensitivity syndrome in a Chinese population.

Ultrasonography of Leprosy Neuropathy: A Longitudinal Prospective Study.

BackgroundPrevious studies have shown that leprosy multi-drug therapy (MDT) does not stop the progression of nerve function impairment. There are no prospective studies investigating the evolution of nerve anatomic abnormalities after treatment. We examined leprosy patients aiming to investigate the evolution of nerve ultrasonography (US) abnormalities and the risk factors for poor outcomes after MDT.Methodology/Principal findingsWe performed bilateral US of the ulnar (U), median (M) and common fibular (CF) nerves in 9 paucibacillary (PB) and 64 multibacillary (MB) patients before and after MDT. Forty-two patients had leprosy reactions (type 1, type 2, acute neuritis) during the study. We analyzed nerve maximum cross-sectional areas (CSA), echogenicity and Doppler signal. Poor outcomes included a post-treatment CSA above normal limits with a reduction of less than 30% (U, M) or 40% (CF) from the baseline, echogenicity abnormalities or intraneural Doppler in the post-treatment study. We found that PB and patients without reactions showed significant increases in CSA at CF, whereas MB and patients with reactions had CSA reduction in some nerves after treatment (p<0.05). Despite this reduction, we observed a greater frequency of poor CSA outcomes in the MB compared to the PB (77.8% and 40.6%; p>0.05) and in the patients with reactions compared to those without (66.7% and 38.7%; p<0.05). There was significantly higher odds ratio (7.75; 95%CI: 1.56–38.45) for poor CSA outcomes only for M nerve in patients with reactions. Poor echogenicity outcomes were more frequent in MB (59.4%) compared to PB (22.2%) (p<0.05). There was significant association between poor Doppler outcomes and neuritis. Gender, disease duration, and leprosy classification were not significant risk factors for poor outcomes in CSA, echogenicity or Doppler.Conclusions/SignificanceUS nerve abnormalities can worsen after treatment despite the leprosy classification or the presence of reactions.

Alterations to antigen-specific immune responses before and after multidrug therapy of leprosy

This study evaluated the impact of leprosy multidrug therapy (MDT) on cell-mediated immunity (CMI) and antibody responses at diagnosis in untreated paucibacillary (PB) (n=15) and multibacillary (MB) patients (n=15) using a panel of Mycobacterium leprae recombinant antigens (rMLs) (CMI: 46f, ML0276, ML2055, leprosy IDRI diagnostic 1 [LID-1], and ML2629, as negative control; serology: LID-1, 46f, 92f, and 33f, as negative control, and phenolic glycolipid I [PGL-I]) and at 2 time points after MDT (PB: 8–20months; MB: 4–22months). At diagnosis, PB patients produced interferon gamma (IFNγ), and MB patients exhibited low/absent response. Shortly after MDT, IFNγ production in PB patients declined except for LID-1; MB patients produced IFNγ to LID-1. Almost 2years after MDT, IFNγ levels declined in PB and MB patients. Most untreated PB patients were seronegative to PGL-I and rML, remaining so after MDT. Most untreated MB patients were seropositive to all antigens, and IgG to rMLs declined after MDT. Reduction in antigen-specific CMI in PB and in antibody response in MB patients may help monitor MDT effectiveness.

Clinical features of relapse after multidrug therapy for leprosy in China

Although the World Health Organization (WHO) has defined relapse in leprosy, it is often difficult to confirm a relapse, especially in paucibacillary (PB) patients. To study features of relapse cases in order to determine the information needed to allow better management of relapses in the leprosy control programme. A retrospective survey by questionnaire was carried out at national level at the end of 2012. There were 40 relapsed patients on register. The clinical form of leprosy was TT5, BT4, BB5, BL13 and LL13. Twenty-eight patients had had a positive skin smear test at the start of MDT, with a BI ranging from 0.83 to 6.0. At the time of completing MDT, the skin smear test remained positive in seven patients. After completion of MDT, other family members of 13 patients were identified as new leprosy patients. All relapse cases showed one or more active skin lesions. There were 33 patients with a positive skin smear test at the time of relapse. A total of 23 patients had a biopsy at the time of relapse, including seven patients with a negative skin smear test. The histological features of relapsed BB-LL patients included granulomas containing macrophages or epithelioid cells with sparse lymphocytes and acid-fast bacilli. The histological features of seven patients with negative skin smears showed epithelioid cell granulomas with dense lymphocytes surrounding the granuloma, but without distinct edema in the dermis. The average interval from completion of MDT to the diagnosis of relapse was 168.5 ± 92.6 months with a range of 21-322 months. During the study, nine patients were tested for rifampicin resistance, but none showed any mutation. Leprosy relapse after MDT usually occurred late and all relapse cases had new active skin lesions. Most patients relapsed with a positive skin smear after previously reaching negative BI status. Relapse with a negative skin smear test should be confirmed very cautiously.

Bullous erythema nodosum leprosum manifesting in the post partum period with unusual features

A 30 year old woman who presented with multiple numb patches on the body was initially diagnosed as borderline lepromatous leprosy and started on multidrug therapy for leprosy. She had an episode of Type 1 reaction during the fifth month of pregnancy. After delivery, she stopped therapy fearing harm to her child and developed an episode of Type 2 reaction. The reaction was unusual in that bullous lesions developed over previous leprosy patches which had initially become indurated, with associated neuritis. Histopathology revealed bullae with intense neutrophilic reaction and strong positivity for acid fast bacilli. There was no response to steroid therapy which was started for the reaction. Thalidomide had to be prescribed after stopping lactation by medical means. She responded dramatically to Thalidomide with regression of cutaneous lesions and neuritis. This patient is being reported as a very unusual manifestation of bullous erythema nodosum leprosum in the postpartum period responding dramatically to thalidomide.

WHO multidrug therapy for leprosy: epidemiology of default in treatment in Agra district, Uttar Pradesh, India.

Aim. To study the magnitude of default, time of default, its causes, and final clinical outcome. Methods. Data collected in active surveys in Agra is analyzed. Patients were given treatment after medical confirmation and were followed up. The treatment default and other clinical outcomes were recorded. Results. Patients who defaulted have comparable demographic characteristics. However, among defaulters more women (62.7% in PB, 42.6% in MB) were seen than those in treatment completers (PB 52.7% and MB 35.9%). Nerve involvement was high in treatment completers: 45.7% in PB and 91.3% in MB leprosy. Overall default rate was lower (14.8%) in ROM than (28.8%) in standard MDT for PB leprosy (χ 1 2 = 11.6, P = 0.001) and also for MB leprosy: 9.1% in ROM compared to 34.5% in MDT (χ 1 2 = 6.0, P = 0.015). Default rate was not different (28.8% versus 34.5%, P > 0.05) in both types of leprosy given MDT. Most patients defaulted at early stage of treatment and mainly due to manageable side effects. Conclusion. The default in standard MDT both for PB and MB leprosy was observed to be significantly higher than in ROM treatment. Most defaults occurred at early stage of treatment and major contribution of default is due to side effects like drowsiness, weakness, vomiting, diarrhea, and so forth, related to poor general health. Although about half of the defaulters were observed to be cured 2.2% in PB-MDT and 10.9% of MB-MDT developed disability. This is an issue due to default. Attempts are needed to increase treatment compliance. The use of specially designed disease related health education along with easily administered drug regimens may help to reduce default.

Clinical Oxidative Stress during Leprosy Multidrug Therapy: Impact of Dapsone Oxidation

This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 µg/mL) and paucibacillary (0.662±0.123 µg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDT-supervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software.

Pulmonary tuberculosis and lepromatous leprosy co-infection in a single individual: A Case report

The concomitant occurrence of the two oldest mycobacterial diseases that is tuberculosis and leprosy in a single individual is not rare but has been infrequently reported. Herein, we report a case of 34-year-old laborer who concomitantly presented with both sputum positive pulmonary tuberculosis and lepromatous leprosy. The diagnosis of the two diseases was made simultaneously, which is again infrequent in literature. The treatment of leprosy warrants screening of individual for tuberculosis because multi-drug therapy for leprosy may lead to acquired drug resistance for rifampicin, which is a mainstem of anti-tubercular therapy.

BCG immunotherapy as an adjunct to chemotherapy in BL-LL patients – its effect on clinical regression, reaction severity, nerve function, lepromin conversion, bacterial/antigen clearance and ‘persister’ M. leprae

Multidrug therapy in leprosy has failed to eliminate the problem of persister bacilli. Clearance of bacterial antigens is extremely slow which could predispose to continued nerve damage even after release from treatment. In the present study the immunomodulatory efficacy of BCG vaccine administered post-MDT in BL-LL leprosy patients was investigated in depth with a view to determining if augmenting chemotherapy with immunotherapy would help in faster clearance of M. leprae/antigens, bring down the level of persisters and minimise the occurrence/severity of reaction and nerve damage. This is a placebo-controlled study in treated BL-LL patients. The patients are matched with respect to age, sex, bacteriological index and history of reaction, stratified and allocated to the two groups. One group (Gr A) received two doses of BCG-MOSCOW (3-33 x 10(5) cells) and the other (Gr B) normal saline (0.85%), injected intra-dermally at 3 month intervals. The Primary outcomes assessed at the end of 6 months were bacterial/antigen clearance, lepromin conversion, granuloma clearance and the occurrence of persisters. The secondary outcomes were clinical regression, occurrence and severity of reaction and changes in nerve functions. A total of 107 BL-LL patients comprised of 49 in Gr A and 58 in Gr B; of which 36 and 42 respectively completed the study as per protocol, and are included in the final analysis. The study findings show that both the primary and the secondary out comes were comparable in the two groups. Two doses of BCG administered post-MDT (Gr A) did not significantly alter the level of persisters or help in hastening the bacterial/antigen clearance, clinical regression of lesions and granuloma clearance. Lepromin conversion rates were also comparable. While the frequency of lepra reaction/neuritis following the intervention was comparable, the severity of reactions was significantly higher in Gr A. On the positive side neural functions assessed by nerve conduction studies showed that deterioration of motor nerve conduction was significantly lower in the BCG arm. Since all patients developing moderate to severe reactions, immediately received a course of corticosteroids, it is possible that timely use of it might have helped.

Multiple median nerve abscesses: A rare presentation of leprosy

A 25 year old male presented with swellings around the left elbow and forearm since 2 years. Examination showed 4 swellings along the course of median nerve over the left arm, elbow and forearm. They were circumscribed, soft to firm nodules with tenderness. There were no cutaneous lesions suggesting of leprosy. Histopathological examination of a biopsy from a swelling showed granulomas in the epineurium suggesting the diagnosis of leprosy neuritis. With these clinico-pathological features diagnosis of median nerve abscesses was confirmed. The patient was treated with multi drug therapy for leprosy and oral steroids.