MDT-MB therapy in paucibacillary leprosy: a clinicopathological assessment

BACKGROUND: The World Health Organization recommends treatment regimens for paucibacillary (PB) and multibacillary (MB) leprosy, which differ in their duration and components. Hence accurate classification of the disease is required. To overcome difficulties in classification Uniform Multi Drug Therapy (U-MDT) has been recommended. AIM : To evaluate the benefit of adding clofazimine to paucibacillary regimens in leprosy patients by measuring clinical and histological resolution. METHODS: Forty-four paucibacillary patients were included in the study. Twenty-two patients were given MDT-PB regimen and the remaining MDT-MB regimen for six months . Skin biopsies were done before the commencement and at the end of treatment. Clinical and histological resolutions were measured according to the standard criteria a laid down. The results were analyzed using Fishers' test and Crammers' V test. RESULTS: Clinical improvement was observed in 90.9% in the MB group as compared to 27.3% in the PB group. Regression in the nerve swelling was observed in 70% in the MB group and in 37.5% in the PB group while histological resolution was observed in 72.8% and 54.5% respectively. CONCLUSIONS: Addition of clofazimine helps to resolve leprosy lesions both clinically and histologically, thus justifying the concept of Uniform MDT regimen for all patients.     

Comparison of two systems of classification of leprosy based on number of skin lesions and number of body areas involved--a clinicopathological concordance study

BACKGROUND AND AIMS: WHO guidelines classify leprosy patients for therapeutic purposes into paucibacillary (PB) and multibacillary (MB) leprosy based on the number of skin lesions. An alternative system of classification has been in practice in Nepal from 1985 onwards, based on the number of body areas involved in patients of leprosy. We attempted a clinicopathological approach for comparison of these two systems of classification in leprosy patients for their ability to demarcate patients into groups of PB and MB leprosy. MATERIALS AND METHODS: The study included 108 leprosy patients (80 males and 28 females). Complete clinical examination and body charting was carried out in each patient noting the count of skin lesions and the number of body areas involved. Slit skin smears and skin biopsies were taken from an active skin lesion in all patients. RESULTS: On analysis, it was observed that there was good clinicopathological correlation between patients with 5 or < 5 skin lesions and 2 or < 2 body areas involved. (Clinical 95% and histological 96%) A similar correlation was also observed in the other group of patients with > 5 skin lesions and > 2 body areas involved, (Clinical 94% and histological 96%). There were almost identical numbers of patients represented in these two groups of classification. CONCLUSIONS: Our findings suggest that patients with involvement of 2 or less body areas can be classified as PB leprosy and those with more than 2 body areas involved can be classified as MB leprosy for the purposes of therapy. The study of areas of involvement in leprosy patients not only provides additional patient information but also adds another parameter as a basis for the study of leprosy patients.     

Tissue and blood superoxide dismutase activity and malondialdehyde level in leprosy

Background Oxidative stress (OS) results from an imbalance between free radical generating and scavenging systems. The end product of lipid peroxidation, malondialdehyde (MDA) serves as a marker of cellular damage. Superoxide dismutase (SOD) traps free radicals and acts as a free radical scavenging system. Objective To study OS indices in paucibacillary (PB) and multibacillary (MB) leprosy in tissues and blood. Materials and methods The study group comprised untreated PB patients (n = 14), untreated MB patients (n = 18) and normal human volunteers (n = 20). SOD activity, MDA level and MDA/SOD ratio were estimated in both blood and tissue. Results Compared with controls, SOD activity in tissues decreased significantly in both PB and MB patients, while SOD activity in erythrocytes decreased significantly only in MB. In addition, MDA levels increased significantly in tissues of both PB and MB patients. Moreover, the mean level of MDA in plasma of MB patients was significantly higher, whereas there was no significant difference in that of PB patients. This study showed significant increase in OS index (MDA/SOD ratio) in tissue of PB and MB patients and in blood of MB patients only, whereas there was no significant difference in OS index in blood of PB patients compared with that in the controls. Conclusion Oxidative stress was observed in both tissues and blood of MB patients and in tissues of PB patients, denoting its crucial involvement in the pathogenesis of leprosy. This can constitute an important tool in prognosis, treatment and control of leprosy.     

The ML flow test as a point of care test for leprosy control programmes: potential effects on classification of leprosy patients

OBJECTIVE: To evaluate the use of the ML Flow test as an additional, serological, tool for the classification of new leprosy patients. DESIGN: In Brazil, Nepal and Nigeria, 2632 leprosy patients were classified by three METHODS:: (1) as multibacillary (MB) or paucibacillary (PB) according to the number of skin lesions (WHO classification), (2) by slit skin smear examination, and (3) by serology using the ML Flow test detecting IgM antibodies to Mycobacterium leprae-specific phenolic glycolipid-I. RESULTS: The proportion of MB leprosy patients was 39.5, 35.6 and 19.4% in Brazil, Nepal and Nigeria, respectively. The highest seropositivity in patients was observed in Nigeria (62.9%), followed by Brazil (50.8%) and Nepal (35.6%). ML Flow test results and smears were negative in 69.1 and 82.7% of PB patients, while smears were positive in 58.6% of MB patients in Brazil and 28.3% in Nepal. In MB patients, both smears and ML Flow tests were negative in 15.6% in Brazil and 38.3%, in Nepal. Testing all PB patients with the ML Flow test to prevent under-treatment would increase the MB group by 18, 11 and 46.2% for Brazil, Nepal and Nigeria, respectively. Using the ML Flow test as the sole criterion for classification would result in an increase of 11.3 and 43.5% of patients requiring treatment for MB leprosy in Brazil and Nigeria, respectively, and a decrease of 3.7% for Nepal. CONCLUSIONS: The ML Flow test could be used to strengthen classification, reduce the risk of under-treatment and minimize the need for slit skin smears.     

Oxidative stress and anti-oxidant status in leprosy patients

Severe oxidative stress has been reported in leprosy patients because of malnutrition and poor immunity. The purpose of this study was to investigate the serum lipid peroxidation products, serum LDH and important free radical scavenging enzymes, i.e. superoxide dismutase (SOD), and catalase and anti-oxidant glutathione levels and total anti-oxidant status, in different types of leprosy patients. The subjects for this study were normal human volunteers (NHVs, n=14), paucibacillary leprosy patients (PB, n=18), untreated MB patients (MB1, n=18), MB patients under treatment (MB2, n=19), and MB patients released from treatment (RFT) (MB3, n=28). The levels of lipid peroxidation product, malondialdehyde (MDA), and LDH increased significantly (p<0.001) in MB (MB1, MB2, MB3) patients, and both gradually decreased with clinical improvement following MDT. The levels of SOD, catalase and glutathione, and the total anti-oxidant status decreased significantly in MB (MB1, MB2, MB3) patients (p<0.001), in comparison with NHVs. They gradually increased with clinical improvement with MDT. There was no significant variation of these parameters in PB leprosy patients in comparison with healthy volunteers. High free radical activity and low anti-oxidant levels observed in MB (MB1, MB2, MB3) leprosy patients indicate that there is an oxidative stress in MB cases, irrespective of the treatment status and suggest a suitable anti-oxidant therapy to prevent possible tissue injury.     

Profile of new cases of childhood leprosy in a hospital setting

A hospital-based prospective study was carried out to assess the frequency of occurrence of leprosy in childhood. Out of 800 patients registered for leprosy, 67 (8.4%) were children aged 4-14 years. The male-to-female ratio was 2.5:1. Family history of leprosy was found in 14.9% of cases. The commonest type of leprosy was BT leprosy (35.8%), followed by BB leprosy (25.4%) and BL leprosy (19.4%). More than half of the patients had more than one lesion. Nerve involvement was noted in 70.1% of cases. Slit-skin smear was positive in 46.3% of cases. Out of 67 children, PB and MB regimens were given to 29 and 38 respectively.     

Clinical study of nail changes in leprosy and comparison with nail changes in diabetic patients

Background Nail changes in leprotic patients are not specific to leprosy, and may be observed in other peripheral neuropathies. Diabetes is one of the diseases that present with nail dystrophy secondary to peripheral neuropathy, vasculopathy, trauma and infections. Therefore, nail changes in diabetic neuropathy are expected to be very similar to that of leprosy. Objectives To evaluate the frequency and pattern of nail changes in Egyptian leprotic patients with the different spectrums of the disease, and to compare nail changes in leprosy with those seen in patients with diabetic neuropathy. Methods The study included 115 leprosy patients and 60 patients with diabetic peripheral neuropathy. Nail examination was thoroughly carried out and various nail changes were recorded including the location of the involved nails (fingers, toes). Results Our study detected similar incidence of nail changes in both multibacillary (MB) (86%) and paucibacillary (PB) patients (86%). Flag sign (alternating horizontal bands of whitish and pinkish discoloration of the nail) observed in our study was not reported before. It was more commonly seen in MB patients (21%) than in PB patients (14%). Our results also revealed that the nail changes were more commonly seen in leprosy patients (86%) than in diabetic patients (68%). Conclusion Nail changes in leprosy are multifactorial, and could be related to one or more of the following: neuropathy, endarteritis, trauma, drugs or superimposed infections. Nail changes in leprosy may be used as an additional clue that helps in the diagnosis.     

Dynamics of impairment during and after treatment: the AMFES cohort

This study investigates the dynamics of impairment during and after multidrug therapy treatment for the patient cohort of the prospective ALERT MDT Field Evaluation Study (AMFES). The impairment status was compared at intake, at release from treatment (rft), and at the time of the latest survey between 24 and 48 months after release from treatment (follow-up). The eye-hand-foot impairment score (EHF score), which is the sum of the WHO impairment grades of the eyes, hands, and feet, was used as tool for comparison. In all, 433 out of the 592 patients (224 PB and 209 MB) completed treatment in time and were assessed at release from treatment. The risk of getting impaired was 4% for the 113 PB and 21% for the 91 MB patients who were initially free from impairment. Out of the 111 initially impaired PB patients, 41% recovered or improved and 13% worsened in EHF score. For the 118 initially impaired MB patients, these figures were: recovery or improvement 43% and worsening 13%. Three hundred and twenty-three out of the 433 patients (158 PB and 165 MB) had a follow-up examination in between the next 24-48 months after rft. The risks of impairment at follow-up were 6% for the 79 PB and 18% for the 77 MB patients without impairment at rft. Out of the 79 PB patients with impairment at rft, 35% recovered or improved and 28% worsened. For the 88 impaired MB patients, these figures were: recovery or improvement 26% and worsening 27%. Patients showed a tendency to compensate EHF score improvement before rft by worsening after rft and vice versa. The first main conclusion is that the impairment status at intake was by far the most important determinant for future impairment. The second one is that the dynamics of impairment were less favourable after rft than before. Little is known about the long-term fate of leprosy patients with irreversible nerve damage and the associated risk of developing severe secondary impairment. Especially in this era of the leprosy elimination goal, we should give this accumulating patient group due attention in research and health policy agendas.     

A study on trend of relapse in leprosy and factors influencing relapse

A retrospective analysis of data pertaining to the rural field operation area of the Central Leprosy Teaching and Research Institute, Chengalpattu, Tamil Nadu, was carried out to determine the magnitude of relapse after MDT and its significance with other variables. The study included 3248 leprosy patients who have successfully completed treatment during 1987-2003, of whom 2892 were PB and 356 MB cases. A total of 58 cases of relapse was reported which gives a crude cumulative relapse rate of 1.78% for the 16-year period of follow-up and the rates for PB and MB were 1.9% and 0.84% respectively. With respect to PB cases, 68% of relapses were reported in the first 3 years of RFT. The person-year relapse rate was highly significant with regard to the number of skin lesions (p<0.0002) and nerve involvement (p<0.0002). The person-year relapse rate did not differ significantly between PB and MB leprosy, male and female, and child and adult cases. RFT year cohort relapse rate reveals that the introduction of MB-MDT regimen for PB leprosy had resulted in the reduction of relapses among PB cases after 1998. The relapse rate with reference to the time gap after RFT reveals that relapse declines with passage of time after RFT. The risk of relapse was very low in both PB and MB leprosy which fact emphasizes that proper counselling about signs and symptoms of relapse during RFT is adequate to combat the problem. A majority of relapses occurred in the first three years after RFT. The number of skin lesions and involvement of nerves were the main risk factors for relapse.     

Perspectives of leprosy patients on MDT services after integration of NLEP functions into primary health care

Sixty-five leprosy patients residing in rural Digapahandi block of Ganjam district were studied during July-August 2001 in order to ascertain their perspectives regarding different MDT services after NLEP functions were integrated into primary health care (PHC) in Orissa after September 1999. They included 43.08% multibacillary (MB) cases and 61.92% paucibacillary (PB) cases. Assessment was done by personal interviews of adult patients and the parents of child cases after verification of their treatment cards at the sub-centre. Patient's knowledge regarding the availability of MDT services under PHC services and utilization of these services were highlighted. Influence of different socio-demographic factors was also studied. Basing on the study results, recommendations were made for sustained NLEP functions through PHC in order to improve the utilization of MDT services, which will help in the elimination of leprosy.     

贵州省新发麻风病患者特征分析

目的了解贵州省低流行状态下新发麻风患者特征,为今后发现更多早期麻风患者,有效降低2级残疾比提供科学的依据。方法采用统一问卷进行现场一对一的调查,并将患者调查问卷和病案信息录入EXCEL表格建立数据库,用SPSS18.0软件进行分析。结果贵州省2012-2018新发的387例麻风患者中,男281例,女106例,男∶女=2.65∶1,14岁及以下患者占4.13%,平均延迟期为43.80个月。周围神经受损主要有尺神经311例(80.36%)、腓总神经176例(45.48%)、耳大神经125例(32.30%),皮损主要有麻木98例(25.32%)、红斑95例(24.55%)、脱眉85例(21.96%)。MB型占75.50%,MB∶PB=3.07∶1,通过比较,麻风的不同型别在性别、年龄和延迟期之间无差异,但少数民族患者的MB型显著性高于汉族(P<0.05),有明确传染源的MB型患者高于不明传染源的(P<0.05),差异均有统计学意义。病期在2年内且无疾残的早期患者为220例(56.85%),以文化程度较高(初中以上)的早期患者为主(70.59%)。不明传染源的患者2级残疾比明显高于有明确传染源的患者,差异有统计学意义(P<0.001),延迟期越长,残疾情况越严重。94.44%的14岁及以下患者均有明确的传染源接触史。结论近年来贵州省新发麻风以多菌型为主,且每年都有儿童患者被发现,仍有局部流行风险,患者延迟诊断情况较严重,急待提升医务人员识别早期麻风能力和患者接触检查质量,实现麻风患者的早期发现。     

Epidemiological trends of leprosy in an urban leprosy centre of Delhi: a retrospective study of 16 years

This study was done by collecting the retrospective data from 1994 to 2009 of patients attending the urban leprosy centre attached to the department of dermatology, STD & leprosy of PGIMER & Dr. R M L Hospital, New Delhi. The data was analysed according to age, sex, type of leprosy, leprosy reactions, deformities and relapse and compared with the national figures by comparison of proportions after taking the national data per 10,000 population. A total of 3659 patients attended our ULC (Urban Leprosy Centre) among which 2741 were male and 945 females (M:F-3:1). 669 patients (18.2%) were children. The data analysed show a gradual decline in new case detection rate with a marginal rise in 2005 and 2008. Percentage of MB cases was falling consistently till 2005 after which it showed an abrupt rise. The incidence of type 1 reaction varied from 21% in 1994 to 10% in 2009 in PB patients and from 6% in 1994 to 8% in 2009 in MB patients. The trend of type 2 reactions in MB patients showed a slow declining trend. MDT completion rate showed an impressive improvement from 56% in 1994 to 90% in 2009. The number of patients revisiting the ULC with features of relapse also showed a decrease in number. The pattern of visible deformities showed an almost constant trend similar to national figures. Improved MDT completion rate helps in reducing the disease transmission, severity, reactions and disabilities.     

Leprosy situation in the slums of Agra City--epidemiological findings

The present article is the result of a study of the leprosy caseload in Agra City and is based on a house-to-house survey conducted during April-July 2003 in 5 areas. During the survey 198,150 persons were examined, and 287 cases were detected, giving a prevalence rate of 14.5/10,000. A majority of them (92%) were new cases, detected and diagnosed for the first time. The patient load was found to be unevenly distributed with comparatively more number of patients in areas such as Jamuna Kinara, Shah Ganj and Lohamandi. Among the 264 newly detected cases, 14.8% were of MB type. Overall deformity of grade > or = 2 was seen in 2.8% of patients--0.4% in PB and significantly high at 18% in MB leprosy. The observations reveal that leprosy is endemic in slum areas of Agra City.     

1990-2018年云南省新发麻风患者畸残情况分析

目的：分析云南省1990-2018年新发麻风患者2级畸残情况。方法：对1990-2018年11010例新发麻风患者资料进行分析。结果：新发病例中2级畸残2647例,2级畸残率24.04%。4006例少菌型患者中2级畸残者1294例（32.3%）, 7004例多菌型患者中畸残者1353例(19.3%)。对其中的2202例畸残者进一步分析,单侧和双侧眼部畸残分别为138例和184例,手部单双侧畸残分别为742例和430例,足部单双侧畸残分别为384例和144例。结论：少菌型（PB）比多菌型（MB）麻风患者畸残比例更高,手部畸残明显高于眼部和足部,手部和足部畸残常呈不对称性。     

Leprosy beyond MDT: study of follow-up of 100 released from treatment cases

Appearance of new skin and/or nerve lesions during or after fixed duration of multidrug therapy (MDT), in leprosy, is not uncommon. It could be a lesion due to leprosy reaction or relapse. Differentiation is easy in classical reactions both clinically and histopathologically. But, difficult in other situations especially when the relapse cases present with features of reaction at the onset. A study was done to find the reasons for released from treatment (RFT) cases to come to clinic and to follow in terms of clinical and neurological activity, leprosy reactions and deformity progression. Out of them, 14 cases and 86 cases had received paucibacillary (PB) and multibacillary (MB) multidrug therapy respectively. Skin lesions either old or new were noticed in 74% cases which might be due to inactivity or activity were noticed in 74% cases which might be due to inactivity or activity in forms of relapse and reaction. Relapse was seen in 26 cases. Out of these, 10 and 16 cases were previously diagnosed as PB and MB cases respectively. PB cases relapsed into MB cases while MB cases relapsed into MB cases. 46 cases presented with either type 1 or type 2 reaction. After declared as RFT, parasthesia in 34 cases, weakness in 18 cases, paresis and paralytic deformity in 6 cases were seen. So, all the RFT cases need regular follow-up, IEC and physiotherapy to prevent deformity and to diagnose relapse and reactions at the earliest.     

SLE患者皮质类固醇治疗前后血清IL－2和TNF－α水平的比较

ＳＬＥ患者皮质类固醇治疗前后血清ＩＬ－２和ＴＮＦ－α水平的比较刘国英①瞿国伟②ＳＬＥ是一种以免疫调节异常为特征的自身免疫性疾病，而免疫调节主要是通过多种细胞因子相互作用实现的。因此，研究ＳＬＥ病人细胞因子变化将有助于阐明该病的发病机理，我们检测了１４...     

Nerve function impairment in leprosy: design, methodology, and intake status of a prospective cohort study of 2664 new leprosy cases in Bangladesh (The Bangladesh Acute Nerve Damage Study).

The Bangladesh Acute Nerve Damage Study (BANDS) is a prospective cohort study designed to investigate epidemiological, diagnostic, therapeutic and operational aspects of acute nerve function impairment in leprosy. The study is based at a single centre in Bangladesh, in an area with a high prevalence of leprosy. The centre, Danish Bangladesh Leprosy Mission, has a well-established vertical leprosy control programme. In this paper, the study design and methodology are described, together with definitions of nerve function impairment (NFI) used in this and subsequent papers. The study recruited 2664 new leprosy cases in a 12-month period. The male:female ratio is 1.25:1, and 17.61% of the cohort are under 15 years of age. In all, 83.33% of the cohort are paucibacillary (PB), and 16.67% multibacillary (MB). However, the MB rate amongst males is 19.72%, and amongst females is 12.85%, despite an equal period of delay to diagnosis. 55% of patients presented for treatment within 12 months of developing symptoms 6.12% of the total number of cases were smear positive, and 36.71% of the MB cases were smear positive. 9.61% of the total number of cases were graded as having World Health Organisation (WHO) disability grade 1, and 5.97% had grade 2. Amongst MB cases, 27.48% had WHO grade 1 disability present, and 18.24% had grade 2 present, compared with 6.04% and 3.51%, respectively, amongst PB cases. A total of 11.90% of the cohort had sensory NFI of any kind, and 7.39% had motor NFI. Ninety patients presented with NFI needing treatment (3.38%), and of these, 61 (67.78%) had silent NFI. MB patients had a prevalence of reaction/NFI needing treatment nearly 7 times higher than PB cases (15.32% amongst MB; 2.30% amongst PB), and males nearly double that of females (5.67% amongst males, 2.96% amongst females). The most commonly affected nerve by function impairment was the posterior tibial (sensory) with 6.46% of nerves affected (9.38% of patients), followed by the ulnar nerve with 3.23% of nerves impaired (5.56% of patients). Future research and publications, building on this foundation, will focus on the following areas: the incidence of NFI and reactive events, the risk factors for developing NFI, and the response to treatment of patients developing acute NFI.     

2235例麻风垂足的分析

目的：了解麻风垂足的患病情况，为制定预防措施提供科学依据。方法：选择江苏11个县市存活的麻风治愈者及现症患者为调查对象，资料输入计算机统计分析。结果：麻风垂足的患病率为15．7％，单足（13．62％）高于双足（2．07％），男性（16．36％）高于女性（13．84％）,现症及复发病人（31．28％）高于治愈者（15．07％），BT、BB型麻风占23．56％及20．96％。麻风病期在5年以内发生垂足的少菌型麻风（72．41％）高于多菌型（50．47％）；发生过麻风反应的患者垂足占33．75％。垂足有足底溃疡（21．21％）、足骨破坏（19．17％）及足畸形（27．43％）多于无垂足的溃疡（15％）、骨破坏（15．09％）及足畸形（20．19％）。989只垂足可通过手术矫治，要求治疗者只占30％。结论：麻风垂足以男性、现症及复发病人多见且以单足为主，垂足发生的足底溃疡及足畸形明显增多，三分之二的垂足失去了手术矫治的机会，70％的患者对垂足的治疗没有信心。麻风垂足的发生与麻风诊断和治疗的延迟、麻风反应及麻风型别的不同有明显的关系。     

Incidence rates of acute nerve function impairment in leprosy: a prospective cohort analysis after 24 months (The Bangladesh Acute Nerve Damage Study)

In this paper, the incidence rates and cumulative incidence of nerve function impairment (NFI) and leprosy reactions over 24 months follow-up of the prospective cohort of 2664 new leprosy cases are presented. Graphs showing the cumulative incidence of NFI relative to time since registration are presented. Hazard ratios (HRs) for the development of NFI for four variables are given. The majority of patients who developed NFI after registration did so in the first year (67% of multibacillary (MB) patients, and 91% of paucibacillary (PB) patients who developed NFI). Thirty-three percent of all MB patients who developed NFI after registration did so in the second year of follow-up. No PB patients developed NFI for the first time in the last 6 months of follow-up. However, seven NFI events occurred amongst PB patients in that period, amongst those who had already had one NFI event. The incidence rate (IR) of NFI amongst MB patients was 24/100 person-years at risk (PYAR), and amongst PB patients was 1.3/100 PYAR. The HR for the development of NFI amongst MB patients compared with PB patients was 16 using univariate analysis. Amongst patients who had long-standing NFI present at registration, the IR was 27/100 PYAR compared with 1.7/100 PYAR amongst those who did not have long-standing NFI. The HR for developing acute NFI amongst those with long-standing NFI present at registration compared with those without was 14 using univariate analysis. When multivariate regression analysis is applied, the apparently significant univariate HRs for sex and age disappeared. The resultant multivariate HR for leprosy group is 8.8, and 6.1 for the presence/absence of long-standing NFI at registration. In all, 142/166 (86%) of all new NFI events were silent, underlining the need for regular nerve function testing. IRs are presented for the four 6-month periods of the 24-month follow-up. They show a clear stepwise reduction over the total period. The IRs amongst MB patients and those with long-standing NFI present at registration are very high at 34 and 41/100 PYAR, respectively, for the first 6 months of follow-up. Even during the final 6-month period, the IR is maintained at a moderately high level (18 and 15/100 PYAR, respectively).