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).     

Delay in presentation, an indicator for nerve function status at registration and for treatment outcome--the experience of the Bangladesh Acute Nerve Damage Study cohort

The objective of our research was to relate delay in presentation in the Bangladesh Acute Nerve Damage Study cohort to intake status and to treatment outcome. The Bangladesh Acute Nerve Damage Study (BANDS) is a prospective cohort study of 2664 consecutive newly registered patients at clinics run by the Danish-Bangladesh Mission Leprosy (DBLM) project in Nilphamari, northern Bangladesh. The 1-year intake began in April 1995. Three-year follow-up for PB cases and 5 years for MB cases was completed in 2001. Delay in presentation in the BANDS cohort is associated with increased signs of nerve function impairment at registration. Individuals presenting with no nerve impairment and maintaining nerve function to the end of follow-up had the shortest mean delays. Individuals presenting with impairment that did not improve during follow-up had the longest mean delays. Discussion focuses on the value of setting a threshold value defining early presentation. Since the WHO Grade 2 disability rate effectively sanctions lengthy delays where there is no impairment, an indicator relating directly to delay is preferred as an indicator for good practice in leprosy control.     

陕西省麻风新发病例基本情况分析

通过全国麻风防治管理信息系统（LEPMIS）收集陕西省2004-2020年麻风病例资料,对新发麻风患者的基本情况进行回顾性分析。研究纳入了305个麻风新发病例,其中男212例,女93例,MB型麻风272例(89.2%),PB型麻风33例(10.82%)。60岁以上患者49例,20～59岁247例,20以下患者9例。100例（32.8%）有家庭内接触史。42例（13.8%）出现麻风反应,247例（81%）出现神经损害,男性神经损伤率高于女性（86.3% vs 68.8%）。218例（71.5%）出现畸残,其中II级畸残122例,I级畸残96例。     

Clinical and electrophysiological evaluation of nerve function impairment following cessation of multidrug therapy in leprosy.

Seventeen multibacillary (MB) and 15 paucibacillary (PB) cases of leprosy who had had regular and adequate multidrug therapy (MDT) were examined clinically and electrophysiologically at periodic intervals for 1 year following cessation of MDT. All the major nerves were assessed for nerve function impairment (NFI). Overall, two MB (13.3%) and three PB (20%) cases showed signs of deterioration clinically and/or electrophysiologically. The nerve conduction (NC) follow-up studies revealed no significant improvement in the sensory conduction in both the MB and PB groups of nerves, whilst motor conduction showed a significant improvement at the first 6-monthly follow-up among the MB group of nerves. At the study onset, sensory impairment (MB = 62%, PB = 25%) predominated over motor in terms of both severity and frequency. The lower extremity was more frequently and severely affected than the upper in both groups of patients. As an individual test, NC measurement proved to be more sensitive in detecting NFI, but the combination of physical palpatation for nerve thickening and graded nylon test (GNT) was closely comparable to measurement of nerve conduction.     

Factors associated with impairments in new leprosy patients: the AMFES cohort.

Data on the importance of the delay between onset of symptoms and registration as a risk factor for impairment are sparse. This study investigates the quantitative relationship between this delay, other risk factors and the impairment status in new leprosy patients. It reports on 592 new leprosy patients enrolled in 1988-1992 in the prospective ALERT MDT Field Evaluation Study in central Ethiopia (AMFES). The influence of the risk factors sex, age, delay, PB/MB classification in relation to BI, and prior dapsone treatment on the impairment status at intake is analysed. Estimates for the delay are based on patient recall. For the risk factors, odds ratios on impairment and on severity of impairment were calculated using both univariate and multivariate logistic regression. The registration delay was 2 years or more for 44% of new patients. The prevalence of impairment (WHO impairment grades 1 and 2 combined) increased continuously from 36% for new patients with a delay of 0-1 year to 81% for new patients with delays of 4 years or more. This prevalence also increased continuously with age; it rose from 26% in children to 80% for the age group 60 and over. In the multivariate regression, the odds ratios for new patients to be impaired were statistically significant for all delay categories (baseline 1-2 years) and age groups (baseline 15-29 years). No statistically significant differences in odds ratios were observed with respect to sex and PB/MB classification in relation to BI. Overall, 31% of new patients presented with WHO impairment grade 1 and 23% with grade 2. The risk on grade 2 also increased with the registration delay amongst the impaired new patients. Relatively few impaired males and relatively few impaired MB patients with a BI value of 3 or higher had grade 2 impairment. Registration delay and age are the main risk factors for presentation with impairment. Reduction of delay in central Ethiopia requires re-thinking of control methodologies. The search for ways to reduce delays in diagnosis and treatment should receive high priority in leprosy research and in leprosy control programmes.     

Nerve thickening in leprosy patients and risk of paralytic deformities: a field based study in Agra, India

This paper examines the extent of nerve thickening among leprosy patients detected in the field in Agra district. All the clinically diagnosed leprosy patients were examined in detailed for thickening of local cutaneous nerves and peripheral nerve trunks. In each case all the major nerve trunks in both upper and lower extremities, forehead and neck were examined for thickening. Nerve thickening was found in 94% of multibacillary (MB) patients and among 52% paucibacillary (PB) patients. Nerve thickening was found to be more in males, in prevalent cases than in new (untreated) cases and increased significantly with age and delay in diagnosis (P<0.001). Visible deformities of grade > or =2 were found in 10% (58/573) of the leprosy patients; paralytic deformity accounted for 78% (45/58). Claw hand alone or in combination was seen in 82% (37/45) of patients with paralytic deformities. Risk (odd ratio) for deformities was observed to be high (15-18 times) with increasing number of nerves among patients with neuritic leprosy but correlated with delay in diagnosis of over 5 years. Likewise, deformities were more often seen in those with skin lesions, provided they had > or =3 thickened nerves. Findings suggest that early detection and treatment is useful in preventing deformities.     

Case detection, gender and disability in leprosy in Bangladesh: a trend analysis.

A trend analysis is presented of all newly detected leprosy cases over an 18-year period (1979-1996) in a highly leprosy endemic area of Bangladesh. A total of 23,678 new cases were registered, with an average of 860 new cases per year in the first 12 years, and increasing to around 3000 in 1996. The male:female (M:F) ratio decreased from 2.3 to 1.4. The proportions of newly detected cases with MB leprosy and of newly detected cases with any disability decreased over time. These reductions were more marked in the higher age groups of both sexes. The reduction in disability was primarily attributable to a decline in grade 2 disability. New case detection rates (NCDR) of all leprosy patients per 10,000 general population increased for males from 3 to 6; and for females from 1 to 4, while the NCDR of MB leprosy decreased in males from 1.4 to 0.6, and in females fluctuated around 0.45. The NCDRs of leprosy patients with disabilities showed an initial decrease in the first period, especially in males, but later showed an increase. The NCDR of males with disability was about twice as high as that of females. Finally, female NCDRs in the ages between 15 and 30 were low by comparison with the male NCDRs at the same time. This may be due to the sociocultural characteristics of the Bangladeshi society, with gender differences in exposure, health seeking behaviour and opportunities for case detection. Operational changes in the control programme have contributed to the changed profile of newly detected cases. This study shows that the application of general population statistics is essential for understanding the dynamics in leprosy control programmes under changing operational conditions. Combining case detection figures with such statistics helps to identify population groups that are possibly not benefiting sufficiently from the services provided, and to clarify the dynamics in control programmes and the future trends and programme requirements.     

Treatment with corticosteroids of long-standing nerve function impairment in leprosy: a randomized controlled trial (TRIPOD 3)

Some leprosy patients with long-standing nerve function impairment (NFI) appear to have responded favourably to treatment with corticosteroids. This study investigated whether patients with untreated NFI between 6 and 24 months duration and who are given standard regimen corticosteroid therapy, will have a better treatment outcome than a placebo group. A multicentre, randomized, double-blind placebo-controlled trial was conducted in Nepal and Bangladesh. Subjects were randomised to either prednisolone treatment starting at 40 mg/day, tapered by 5 mg every 2 weeks, and completed after 16 weeks, or placebo. Outcome assessments were at 4, 6, 9, and 12 months from the start of treatment. 92 MB patients on MDT were recruited, of whom 40 (45%) received prednisolone and 52 (55%) placebo treatment. No demonstrable additional improvement in nerve function, or in preventing further leprosy reaction events was seen in the prednisolone group. Overall, improvement of nerve function at 12 months was seen in about 50% of patients in both groups. Analysis of subgroups according to nerve (ulnar and posterior tibial), duration of NFI, and sensory and motor function, also did not reveal any differences between the treatment and placebo groups. There was however, indication of less deterioration of nerve function in the prednisolone group. Finally, there was no difference in the occurrence of adverse events between both groups. The trial confirms current practice not to treat long-standing NFI with prednisolone. Spontaneous recovery of nerve function appears to be a common phenomenon in leprosy. Leprosy reactions and new NFI occurred in a third of the study group, emphasizing the need to keep patients under regular surveillance during MDT, and, where possible, after completion of MDT.     

Assessing socio-economic factors in relation to stigmatization,impairment status,and selection for socio-economic rehabilitation: a 1-year cohort of new leprosy cases in north Bangladesh

The current leprosy elimination strategy focuses almost exclusively on delivery of leprosy diagnostic services and multi-drug treatment (MDT). However, the specific problems of people newly diagnosed with leprosy or cured with MDT primarily relate to impairment of nerve function and social and economic consequences of the diagnosis of leprosy. This study was carried out to investigate the relation between socio-economic factors and the development of nerve impairments and stigma. In addition the relation between socio-economic factors and selection for socio-economic assistance was studied. The study population was a cohort of 2364 newly diagnosed people with leprosy in rural Bangladesh in 1996, including 42.5% women, with an overall mean age of 31.4 years. Three hundred and sixty people (15.2%) had WHO grade 1 or 2 disability identified at diagnosis, and 50 (2.1%) had stigma identified on interview at home visit conducted within one month of diagnosis. One hundred and eighty-eight people (8%) were selected for specific assistance for rehabilitation, primarily interest-free loans for income generating activities or vocational training. Factors independently associated with WHO grade 1 or 2 disability at diagnosis were multibacillary (MB) classification, adult status, and manual occupations. Smear positivity, female sex, and the presence of dependents were associated with an increase in the experience of stigma. The presence of nerve impairments and stigma, as well as several indices of poverty were clearly associated with selection for inclusion in an integrated program for socio-economic assistance. An increased focus by leprosy services on the socio-economic factors associated with poorer physical and social outcomes is recommended. Where adequate finances and trained staff are available, efforts could be made to identify those at higher risk of poor outcomes, and to provide or to mobilize appropriately targeted socio-economic interventions.     

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.     

A study on the impact of FD-MDT on 200 leprosy patients

A study was carried out from June 1999 to June 2001 to assess the impact of fixed duration multidrug therapy (FD-MDT) in newly detected cases of leprosy in terms of clinical and neurological improvement and changes in the bacillary index of skin smear for AFB. 200 new leprosy cases (both PB & MB) were started on FD-MDT. Of these 200 cases, 16 were of pure neuritic leprosy. After treatment, out of 184 cases with typical skin lesions of leprosy, all 26 PB cases showed inactivity of skin lesions, and, of the remaining 158 MB cases, 40.5% showed inactivity and 59.5% showed complete resolution of skin lesions. Out of 68 skin smear-positive cases, 42 cases with a BI of < or = 3 became smear-negative, while others showed gradual fall in the BI. Such heavily bacilliferous cases were continued with treatment for 1 more year to prevent relapse. As FD-MDT alone does not cure established sensory and motor impairment, it did not show any change in 19% of the patients presented with permanent sensory motor disturbance. FD-MDT prevents progression of sensory/motor disturbance.     

641例麻风患者上肢神经损害的分析

为了解麻风患者上肢神经损害的状况，选择兴化市存活的麻风治愈者及现症患者1575人为调查对象。结果显示麻风患者上肢神经损害的发生率为40．7％，单侧损害（23．17％）高于双侧（17．52％），现症及复发病人（69．23％）高于治愈者（40．46％），多菌型（55．94％）高于少菌型（38．46％）。尺神经损害为36．63％，正中神经为16．95％，桡神经为2．35％，爪形指继发关节强直为73．03％，神经损害与麻风反应有关的为43．37％。兴化市麻风上肢神经损害多见于现症及复发病人以单侧损害为主，尺神经损害第一，其次为正中神经、桡神经，2／3的神经损害是不可逆的。因麻风诊断的延迟、麻风反应及麻风型别的不同，上肢神经损害的差异非常明显。     

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.     

The pattern of leprosy-related neuropathy in the AMFES patients in Ethiopia: definitions, incidence, risk factors and outcome

The ALERT MDT Field Evaluation Study (AMFES) began in 1988 and followed patients prospectively for up to 10 years after release from treatment (RFT). This paper presents the findings from this cohort with regard to neuropathy and nerve damage. Five hundred and ninety-four new cases of leprosy are included in the study, 300 multibacillary (MB) and 294 paucibacillary (PB) cases. Fifty-five percent of patients had some degree of impairment at diagnosis and a further 73 (12%) developed new nerve function impairment (NFI) after starting multiple drug therapy (MDT). The overall incidence rate for neuropathy was 39 episodes per 100 PYAR in the first year after diagnosis, gradually declining to 12 episodes per 100 PYAR in the sixth year. In those patients without impairment at diagnosis, the incidence rate of neuropathy was 25 episodes per 100 PYAR for MB cases and 11 per 100 PYAR for PB cases in the first year; in 33% of MB cases whose first episode of neuropathy occurred after diagnosis, that first episode took place after the first year, or after the normal period of treatment with MDT. Seventy-three patients with neuropathy developing after diagnosis are reported more fully: 34 (47%) had only one nerve involved and of these 25 (73%) had a single, acute episode of neuropathy. Nine (27%) had further episodes. Thirty-nine (53%) had more than one nerve involved and of these 16 (41%) had a single, acute episode, while 23 (59%) had further episodes. The terms 'chronic' and 'recurrent' neuropathy are defined and used to describe the pattern of neuropathy in those with repeated attacks. In patients with no impairment at the start of the study, treatment with steroids resulted in full recovery in 88% of nerves with acute neuropathy but only 51% of those with chronic or recurrent neuropathy. The median time to full recovery from acute neuropathy was approximately 6 months, but in a few cases recovery occurred gradually over 2-3 years. Severe neuropathy was less likely to be followed by a complete recovery than mild or moderate neuropathy. Forty-two percent of nerves with acute neuropathy that were not treated with steroids also fully recovered. In the group of patients who were thought to have old, permanent impairments at diagnosis, full recovery of nerve function occurred in 87/374 (23%) of the nerves involved. The overall outcome is illustrated by examining the average EHF score for groups of patients. Patients with no new neuropathy after diagnosis show a gradual improvement in their EHF score, while those with any episodes of neuropathy after diagnosis show a gradual deterioration after completion of MDT. Possible explanations for these findings are discussed. Risk factors for neuropathy, for chronic and recurrent neuropathy, and for a poor outcome 5 years after release from treatment, are examined. Impairment at diagnosis was the main risk factor for a poor outcome, accompanied by the occurrence of chronic/recurrent neuropathy or a reversal reaction.     

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 clinical prediction rule for nerve function impairment in leprosy patients-revisited after 5 years of follow-up

Nerve function impairment (NFI) commonly occurs during or after chemotherapy in leprosy. We previously described a clinical prediction rule to estimate the risk of NFI occurring within 2 years of diagnosis, based on 2510 patients who are followed up in the Bangladesh Acute Nerve Damage Study (BANDS). This prediction rule assigns new leprosy patients to one of three risk groups based on leprosy group and the presence or absence of NFI at registration. Updated data with up to 5 years of follow-up showed that 95% of all NFI occurred within 2 years. This study confirms the validity of the rule and supports the conclusion that there is little value for the detection of NFI in extending follow-up beyond 2 years.     

Patterns of erythropoiesis and anaemia in leprosy

A total of 128 leprosy patients were investigated for the morphological type of anaemia, the underlying disturbances in iron metabolism and patterns of erythropoiesis and other cytomorphological changes in the bone marrow. The anaemia was a mild to moderate degree in paucibacillary (PB) leprosy, while in multibacillary (MB) leprosy it was of a severe degree. Iron deficiency was observed in only a few patients. Impaired iron utilization as observed in a anaemia of a chronic disorder was a common finding in MB leprosy (41.7%) and more so in new cases (50%). Megaloblastic erythropoiesis was also more frequent in MB leprosy (45.2%) as compared to PB leprosy (16%), accounting for the severe degree of anaemia in the former type. In 17.2% of the total patients (MB, 21.4%; PB, 9%) both megaloblastic erythropoiesis and features of impaired iron utilization were observed in bone marrow. Disturbances in iron metabolism and erythropoiesis were also observed but to a lesser degree in patients receiving specific antileprosy treatment. Irrespective of the type of disease and duration of treatment, increasing frequency of acid-fast bacillia (AFB) positivity and granulomas was observed in the bone marrow with an increasing severity of anaemia.