Twelve months fixed duration WHO multidrug therapy for multibacillary leprosy: incidence of relapses in Agra field based cohort study.

Background & objectives: The reported low relapse rates after 24 months multidrug therapy (MDT) for multibacillary leprosy (MB) led to the recommendation of reducing duration of therapy to 12 months. However, only a few reports exist on long term follow up data after 12 months fixed duration therapy (FDT). The present study was done to assess the incidence of relapse in MB leprosy patients after 12 months treatment. Methods: The leprosy patients detected in field surveys during 2001-2006 in Agra district, Uttar Pradesh, India, were put on WHO-MDT and followed up for treatment completion, relapse, reactions and development of disability. The assessment was done clinically by following up the patients until January 2011. Data collected were analyzed for risk and survival analysis. Results: The incidence of relapse was found to be 1.97/100 person years of follow up. The incidence of relapse by age (34 yr vs >34 yr), sex (male vs female), delay in detection (<36 months vs >36 months) and smear status (smear +ve vs -ve) was not found to be significantly different but patients with no nerve involvement were observed to have significantly higher relapses than those with three or more nerve involvement (P<0.05). Similarly, borderline-borderline and BB with reaction (BB/BBR) patients were observed to have significantly high relapses than among those with borderline tuberculoid or BT with reaction (BT/BTR) or borderline lipromatous/lepromatous/neuritic (BL/LL/N) type of leprosy (P<0.01). Interpretation & conclusion: From the observations in the study, it can be suggested that relapses occur in 12 months FDT and almost as much as reported in 24 months FDT for MB leprosy. Although, early relapses may be due to insufficient treatment, late relapses may be due to persistent dormant mycobacteria. However, a study relating to immunological response of treatment and change in immunological profile relating to the occurrence of relapses and its clinical correlates may suggest better information on causes of relapses.

Leprosy Scenario in Agra : Epidemiological Observations From Rapid Population Survey 2004-06.

This study based on rapid survey methodology examining 17.86 lakhs population revealed that leprosy prevalence in Agra District is 6.1/10,000 during 2004-06, with 97.2% of the cases detected for the first time. Although leprosy is still endemic but all the leprosy indicators have shown positive change since last survey in 2001-03. The results seem promising to achieve elimination target (<1/10,000) since prevalence/10,000 population declined from 16.4 in 2001-03 to 6.1 in 2004-06, MB rate from 22.3 to 17.1, Mean duration of disease at detection (months) from 32.3 to 22.9, per cent new cases increased from 88.2% to 97.2% and visible disability (Grade >2) rate declined from 4.8% to 2.36% over this period. The data on patients with incomplete history of treatment (prevalent) but having active disease indicate that only about 3% (31/1090) had approached the health center for treatment. Of these 31 patients, 29% defaulted from treatment and still have active disease and 75.2% (23/31) had MB disease indicating a pattern of late reporting to health system. This study suggests that repeat surveys are useful to detect cases for treatment and seems the key to achieve leprosy elimination or even eradication at district level in all endemic districts.

Advances in the treatment of reactions in leprosy.

Morbidity in leprosy is almost always due to reactions. Similarly, to a great extent, deformities in leprosy are the consequence of reactions occurring both in borderline patients (type 1 or reversal reactions) and in lepromatous patients (type 2 or ENL reactions). Over the last three decades, work has centred around finding who are prone to getting the reactions, identifying the risk factors and improving the management of reactions in order to alleviate quickly the suffering and prevent and reverse nerve damage consequent to reactions. Though several new drugs have been tried and found somewhat useful, corticosteroids and thalidomide continue to be the mainstay in the management of leprosy reactions. A brief review of the current understanding is presented.

Is increasing MB ratio a positive indicator of declining leprosy?

In recent years, an increasing MB ratio-trend has been seen in most state reported leprosy data in India and elsewhere. The programme of leprosy all over the world has been integrated with general health system (GHS). This has given rise to gross under reporting of leprosy cases and increasing MB ratio. This paper examines this critical issue and attempt to find out the causes of this trend. The findings suggest clearly that increasing MB ratio is the result of early cases of leprosy being missed out. This can be to the extent of 73% when MB ratio is reached to 47.5%.

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.

Pulsed corticosteroid therapy in patients with chronic recurrent ENL: a pilot study.

A pilot study has been undertaken to compare the efficacy of small dose pulsed betamethasone therapy with need based oral steroids in chronic recurrent erythema nodosum leprosum (ENL) patients. Though this mode of therapy was well tolerated, no advantage with intermittent steroid administration was observed. This could have been on account of small dose of steroid given monthly. Treatment of chronic recurrent erythema nodosum leprosum (ENL) patients continues to be unsatisfactory, particularly, because of nonavailability of thalidomide. Though corticosteroids are effective in suppressing all the manifestations and even restoring partially or fully the functional impairment, their side effects and dependence are equally troublesome. Based on (a) the reported efficacy and safety of intermittent use of corticosteroids in several immune complex mediated disorders (Cathcart et al 1976, Kimberly et al 1979), Liebling et al 1981 and Pasricha & Gupta 1984) and (b) ENL (type II) reactions having similar pathology, a pilot study has been undertaken to see the efficacy and the tolerance of pulsed steroids in chronic ENL patients.

Study of low productive value of rapid survey as a means of leprosy case detection in Kanpur urban project.

A study was undertaken in Kanpur city to identify the reasons for low yield of rapid survey in leprosy case detection and to intervene to overcome the shortcomings. By a random cluster sampling method, 200,000 persons were selected for the study. Rapid survey was undertaken in half the area and in another half similar survey was undertaken after additional inputs. The additional inputs were staff training, IEC activities, changing of the survey timings and addition of a female worker to the survey teams. The proportion of the population enumerated population showed a significant rise (from 58.35% to 72.21%) in the test area with additional inputs. The number and the type of cases detected did not show any difference. Significantly, addition of female workers to the team did not improve the proportion of the female population examined or of female cases detected.

Protective sensibility--its monofilament nylon threshold equivalents in leprosy patients.

An attempt has been made to definite the levels of "protective sensibility" in terms of perception thresholds to monofilament nylon induced touch/pressure stimuli. Certain problems were observed while interpreting the observations. There appears to be a range of threshold values instead of a clear cut-off point. We suggest that a monofilament nylon stimulus two times the normal threshold value for that patient be taken as cut-off point. This will make the observations of Birke and Sims (1986) and Hammond and Klenerman (1987) reasonable without having any need to exclude the cases who defy the boundaries laid by them. Since the genesis of plantar ulcer is multifactorial, it appears logical to include all patients who have a certain degree of hypoaesthesia, for special ulcer care program. The likely problems while using monofilament nylons in the field and their possible solutions have also been outlined.

Efforts in diagnosing early leprosy using serological techniques.

Skin scrapings obtained from the lesions of leprosy patients of all types showed 96% positivity to the serum antibody competition test using monoclonal antibody (ML04)to 35 kDa antigen of Mycobacterium leprae. Further, in vitro culture of full thickness skin biopsies from lepromatous patients were noted to release IgG antibodies to M. leprae with a peak antibody response at 48 h. The significance of this local antibody response to Μ. leprae in skin has been discussed for its possible use in diagnosing early leprosy.

Sensory functions in limbs of normal persons and leprosy patients with peripheral trunk damage.

The threshold to touch was tested in hands and feet of normal persons using Semmes-Weinstein graded monofilament nylons. The minimum stimulus to which response could be elicited was nylon number 3.61 in palms and 4.31 in soles. These numbers relate to the logarithm of the force applied, 3.61 corresponding to 0.217 gm force and 4.31 to 2.35 gm force respectively. The area of pain insensitivity complained by the patient more or less corresponds to that revealed by objective testing. It was interesting to observe that loss of pain sensitivity was confined to a smaller area compared to touch and thermal insensibility in the part innervated by the same nerve trunk.

Bioavailability of dapsone on oral administration of Dapsomine--a comparative evaluation.

This study describes a comparative evaluation of dapsone kinetics in humans on administration of Dapsomine, a capsule containing dapsone 100 mg dispersed in oily-base suspension of clofazimine 50 mg. Seven untreated lepromatous leprosy patients were given one capsule of Dapsomine a day for seven days and the pharmacokinetics parameters in this group were compared with those from another group of seven patients who received dapsone 100 mg and clofazimine 50 mg separately. There were no statistically significant differences in parameters such as peak dapsone plasma concentration (Cmax), basal plasma level (C24h), time to peak level (tmax), absorption half-life (t1/2 alpha), elimination half-life t1/2 beta) and areas under plasma concentration-time curves (AUC0-8h) and AUC0-24h) between the two groups.

A clinico-bacteriological profile of leprosy in children.

Clinico-bacteriological profile of 106 leprosy patients below 15 years of age was studied. Majority of the patients were males and fell in the 10-15 years age group (p less than 0.01). Nearly 89% had not received any prior treatment because of financial constraints. Seventy per cent gave a positive history of contact with adult patients who were mainly of the lepromatous variety (p less than 0.01). Skin lesions were present in 103 cases, mainly on the exposed areas and their number was found to increase significantly with advancing age (p less than 0.01). These lesions were hypopigmented patches in 71% of the children and erythematous in the rest. Cutaneous sensations were affected in most of the patients while nerve thickening was observed in 45. Positivity of the skin smears increased significantly as the number of skin lesions per patient increased (p less than 0.05). With advancing age, the disease moved from the tuberculoid end of the spectrum towards the lepromatous end (p less than 0.01).

Dermatoglyphics in leprosy: (III) Creases of palm.

Palmar configurations of triradii and creases of 100 leprosy patients [50 lepromatous (BL/LL) and 50 tuberculoid (BT/LL)] were compared with those of 100 normal persons selected from families of these patients. The patterns of position of triradii were similar in controls and leprosy patients as such. But, the patterns in the two types of leprosy patients were different. As for palmar creases patterns, there was significant difference between those of controls and patients, double radial base crease occurring more often in patients. However, the differences between the two types of patients were not statistically significant.