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.

The treatment of acute nerve function impairment in leprosy: results from a prospective cohort study in Bangladesh.

In this paper, the outcome of 132 patients having acute nerve function impairment (NFI) is reported at 4 and 12 months after the start of prednisolone treatment. In all, 68% of sensory nerves and 67% of motor nerves showed improvement at 12 months, with no statistical difference in responsiveness of various nerves to prednisolone. Duration and severity of impairment were not found significant predictors of treatment outcome. A core of 32% of impaired nerves did not respond to prednisolone, and 12% of impaired nerves had functional deterioration despite treatment. The mean eye-hand-foot (EHF) score improved from 2.02 to 1.33 in the treatment group (median score improved from 2 to 1). Approximately one-third of all patients requiring prednisolone treatment did not receive it, an important reason being that some patients developed new NFI against a background of chronic impairment, and were thus overlooked. The 'unjustly untreated' group of patients had a spontaneous sensory nerve function improvement rate of 62% and a motor nerve function improvement rate of 33% at 12 months from onset of NFI. The EHF score showed no statistically significant improvement.

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).

A clinical prediction rule for nerve-function impairment in leprosy patients.

BACKGROUND: Nerve-function impairment (NFI) commonly occurs during or after chemotherapy in leprosy and is the key pathological process leading to disability and handicap. We describe the development of a simple clinical prediction rule for estimating the risk of NFI occurrence. METHODS: New leprosy cases who presented to a centre in Bangladesh were recruited and followed up for 2 years in a field setting. We used multivariable regression analysis by Cox's proportional hazards model to identify predictive variables for NFI. Discriminative ability was measured by a concordance statistic. Internal validity was assessed with bootstrap resampling techniques. FINDINGS: 2510 patients were followed up for 2 years, 166 developed NFI. A simple model was developed with leprosy group (either paucibacillary leprosy [PB] or multibacillary leprosy [MB]) and the presence of any nerve-function loss at registration as predictive variables. Patients with PB leprosy and no nerve-function loss had a 1.3% (95% CI 0.8-1.8%) risk of developing NFI within 2 years of registration; patients with PB leprosy and nerve-function loss, or patients with MB leprosy and no nerve-function loss had a 16.0% (12-20%) risk; and patients with MB leprosy with nerve-function loss had a 65% (56-73%) risk. INTERPRETATION: Our prediction rule can be used to plan surveillance of new leprosy patients. Patients at low risk of NFI may need no follow-up beyond their course of chemotherapy (6 months); patients with intermediate risk need a minimum of 1 year of surveillance; and patients with high risk should have at least 2 years of surveillance for new NFI. Current recommendations for surveillance of patients with leprosy (for the duration of chemotherapy only) exclude an important group of patients who are at risk of developing NFI after completion of treatment.

Reliability of Semmes Weinstein monofilament and ballpoint sensory testing, and voluntary muscle testing in Bangladesh.

The reliability of methods of testing nerve function is important, since diagnostic decision making is a direct function of the quality of the test. Three methods of nerve function testing were investigated at the Danish Bangladesh Leprosy Mission (DBLM) in north Bangladesh, and assessed for inter-observer reliability. The three methods were 1) ballpoint pen test (BPT) for sensory function; 2) graded Semmes Weinstein monofilament test (SWM) for sensory function and 3) voluntary muscle testing (VMT) for motor function. The weighted kappa (kappa w) statistic was used to express inter-observer reliability. Using this statistic, 0 represents agreement no better than random, and 1.0 complete agreement. kappa w values of > or = 0.80 are reckoned to be adequate for monitoring and research. Fifty-three patients were tested, a Senior physiotechnician acting as 'gold standard' against whom four other staff physiotechnicians were assessed. All three testing methods were found to have minimal inter-observer variation, with the kappa w for inter-observer agreement using BPT being 0.86, the SWM 0.92, and VMT 0.94. It is concluded that in trained and experienced hands, all three methods are reliable and repeatable to a level allowing confident use of results obtained in monitoring and research.

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.

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.

Knowledge, attitude and practice regarding leprosy and tuberculosis in Bangladesh.

A small survey was carried out in two areas of northern Bangladesh to assess and compare the level of knowledge, attitude and practice towards leprosy and tuberculosis (TB) among two communities that differed widely in the amount of health education received about these diseases. The results indicate that without a health education programme, levels of knowledge about the cause and treatability of the diseases are poor, worse for leprosy than TB, with correspondingly negative attitudes. Only 16% of the respondents in the 'uninformed' area mentioned 'skin patch' in a question about what they knew about leprosy; and only 44% mentioned 'cough' as a symptom of TB. In the area that had received health education, 90% mentioned, respectively, 'skin patch' and 'cough'. Seventy-eight percent of the respondents would not buy goods from a shopkeeper known to have leprosy, 76% if he had TB in the uninformed area; but in the community who had received health education the proportions were reversed, with three-quarters agreeing to purchase from a diseased shopkeeper. The implications of these findings for the DBLM and National Health Education programmes are discussed.

Expenditure and loss of income incurred by tuberculosis patients before reaching effective treatment in Bangladesh.

This small study undertook to assess the economic consequences of developing tuberculosis (TB) among patients presenting to the TB clinic run by the Danish Bangladesh Leprosy Mission in NW Bangladesh. The loss of income resulting from the illness, and the actual expenditure incurred by medicines and doctor's fees before registration for treatment, were estimated and totalled for 21 patients serially registered at the clinic. The results showed a mean financial loss to the patient of US$ 245-an exorbitant sum for a village Bangladeshi. Perhaps economic deprivation suffered by TB patients could be used as a measure of success of the programme.

Tuberculosis control is good for established leprosy programmes.

Tuberculosis (TB) control was introduced into part of the Danish Bangladesh Leprosy Mission's large leprosy control programme in 1994. This was in line with the Government's policy of combining leprosy and TB control. We report our experience with integration. Leprosy case-finding has increased during the period, and staff satisfaction and morale has also risen despite the larger workload. We observed that the field work skills of leprosy workers was brought to bear in a very positive way on TB control. TB patients suffer considerable impoverishment as a result of their illness, paralleling the social dehabilitation often seen in leprosy sufferers. TB control is good for established leprosy programmes.

Field treatment of acute nerve function impairment in leprosy using a standardized corticosteroid regimen--first year's experience with 100 patients.

In this study, a fixed regimen of prednisolone for the treatment of acute nerve function impairment (NFI) in leprosy patients was developed and introduced at field level in one area (Thakurgaon) of the Danish-Bangladesh Leprosy Mission's field in NW Bangladesh. The assessment, management and follow-up of patients was undertaken by leprosy control supervisors and physiotechnicians. One hundred patients were treated and followed up 6-8 months after completion of a 4-month course of prednisolone. At a level of change of 2 points (where a change of at least 2 points in the motor/sensory score was taken to indicate a change of status, i.e. full or partial recovery, or deterioration), 42/65 (64.6%) patients with sensory loss experienced some sensory recovery at completion of prednisolone treatment, and 40/65 (61.5%) at 6-8 months' follow-up. 41/85 (48.3%) of patients with motor loss experienced improvement, and 42/85 (49.4%) at follow-up. Analysis of the mean scores at start of prednisolone treatment, completion and at follow-up using Student's t-test showed highly significant (p < 0.001) differences between scores before and after treatment. The benefit is maintained as seen after a period of 6-8 months follow-up. It was concluded that treatment of acute nerve function impairment at field level by paramedical workers, using a standardized regimen of prednisolone is feasible, practical and effective.

Nerve function impairment in leprosy at diagnosis and at completion of MDT: a retrospective cohort study of 786 patients in Bangladesh.

This retrospective cohort study includes all new leprosy patients registered for multidrug therapy (MDT) in 1990 at the Danish-Bangladesh Leprosy Mission project in Bangladesh. The main objective was to determine the extent of nerve-function impairment (NFI) at diagnosis and at completion of MDT, and to identify opportunities for intervention and their relative impact on the prevention of disabilities (POD). A total of 786 patients were included; 486 males and 300 females. There were 315 PB, and 471 MB patients. In terms of the WHO leprosy disability grading system, at the time of diagnosis 31/315 (9.8%) had grade 1 or grade 2 disability in the PB group, and 177/471 (37.6%) in the MB group. The incidence rate of NFI during MDT was 3.5 per 100 person years at risk (PYR) in the PB group, and 7.5 per 100 PYR in the MB group. In the MB group 37 (7.9%) previously normal patients sustained NFI during MDT, whilst 19 (4.0%) with NFI at diagnosis showed complete recovery at completion of MDT. The most commonly involved nerves were the ulnar (motor function) and the posterior tibial nerves (sensibility). Reversal reactions were observed in 0.6% of the PB patients during MDT, giving an incidence rate of 1 per 100 PYR. The percentage of MB patients diagnosed with reversal during MDT was 14.2%, giving an incidence rate of 6 per 100 PYR. The percentage of MB patients diagnosed with ENL during MDT was 2.1%, with an incidence rate of 1 per 100 PYR. It was concluded that early detection of new cases of leprosy would prevent disabilities in more than 30% of all patients, thus having the highest impact in the quest for the prevention of disabilities. POD activities during and after MDT will prevent disabilities in approximately 10% of all cases. This study also indicates that treatment with prednisolone is effective and should be available at field level for all patients with recent NFI.

Active surveillance in leprosy: how useful is it?

In this paper, active surveillance is compared with self-reporting as a method of detecting new nerve function loss in leprosy patients who have completed multidrug therapy (MDT). Five hundred and three patients were selected according to new surveillance guidelines in one part of the Danish-Bangladesh Leprosy Mission leprosy control project working area. Surveillance coverage of 71% was achieved in a 7-month period. During this time, 10 released-from-treatment (RFT) patients from among the study group were found to have acute nerve damage requiring prednisolone treatment. Out of the 10, only 2 were detected actively; the remaining 8 self-reported. It is concluded that health education given at RFT time is effective in motivating patients to self-report with acute nerve damage, and that the time spent on active surveillance could have been better used in other activities, i.e., case detection. As a result of these findings, active surveillance has been abandoned in the leprosy control project.

Estimating the size of the leprosy problem: the Bangladesh experience.

Assessing the size of the leprosy problem in a country is an important but difficult issue for the purpose of programme planning. Different methods have been proposed but often estimates have proved to be very different from reality. We have attempted to address this issue in Bangladesh, a country where official estimates are more than 5 times greater than the registered number of leprosy cases. A combination of methods, including surveys, data from leprosy control programmes and local knowledge based on the Delphi techniques have been combined to construct an estimate of the total number of cases in Bangladesh. This figure (173,196) is only 10% greater than the official estimate (136,000). It will be possible over the next few years to see how close this figure is to reality through data obtained from the National Leprosy Control Programme which is now rapidly developing to cover the whole country.