Detection of previously undetected leprosy cases in Firozabad District (U.P.), India during 2006-2009: a short communication.

OBJECTIVES: This study was initiated to assess the extent of undetected (new) leprosy cases in Firozabad District of U.P. METHODS: A sample survey of more than 980,000 people was undertaken in nine blocks of the district during October 2006 to March 2009, using a household questionnaire and a cross section survey. RESULTS: A total of 774 previously undetected cases were detected (7.57 NCDR/10,000 population) over the 2.5 year period of the survey. The characteristics of previously undetected cases are described by age, sex, classification, urban/rural residence and disability. CONCLUSION: There are many undetected leprosy patients in the community. Active surveys can help in detecting previously undetected cases. The current programme is based on information, education and communication (IEC) to encourage case reporting. IEC activities should be designed in such a way that people can suspect leprosy and are self-motivated to know about free treatment, its availability, and effectiveness.

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.

Absence of nucleotide-binding oligomerization domain-containing protein 2 variants in patients with leprosy and tuberculosis.

Crohn's disease-associated NOD 2 variants (Arg702Trp and 3020insC) were found to be monomorphic (wild), and 7 subjects were heterozygous for Gly908Arg SNP in 263 patients with tuberculosis, 260 patients with leprosy and 270 healthy controls residing in northern Indian states. This is the first report to suggest the minimal role of these variants in susceptibility/resistance to TB and leprosy in this population.

Induction of lepromin reactivity in cured lepromatous leprosy patients: impaired chemokine response dissociates protective immunity from delayed type hypersensitivity.

Delayed Type Hypersensitivity (DTH) and protective immunity are thought to be tightly linked. Remarkable similarity exists between their cellular and immune mechanisms. However, their dissociation is also well known. Here we investigate the immunological mechanisms relevant for their dissociation in a group of non-relapsing cured lepromatous leprosy (CLL) patients. In these patients, using lepromin reaction as a model system of DTH we report critical role of tissue chemokine response in synchronous manifestation of these linked phenomena. Results indicate elevation of the threshold of tissue chemokine induction thus dissociating DTH from protective immunity in lepromin -ive CLL patients. We also show that the DTH anergy in these subjects is not an absolute one but depends on the strength of the stimulus. Our data provide insights into the intricate relationship between DTH and immunity and highlight the persistent presence of effector immune mechanisms involving these two pathways in apparently unresponsive lepromatous leprosy patients.

Two microbiological relapses in a patient with lepromatous leprosy.

A lepromatous patient treated with dapsone in the pre-MDT era to the point of smear negativity (> 6 years), relapsed 5 years after stopping treatment. He was then put on WHO-MDT for multibacillary (MB) leprosy, and was treated again; he had negative slit skin smears (3 years). He again presented with a relapse of leprosy 17 years after stopping treatment, and this time he presented with borderline leprosy in reaction.

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 > or = 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.

Increased level of urinary nitric oxide metabolites in leprosy patients during type 2 reactions and decreased after antireactional therapy.

OBJECTIVES: To assess the urinary nitric oxide metabolites in lepromatous patients in ENL (type 2 reactions) and to compare these metabolites after subsidence of reactions following antireactional therapy. Further to compare the levels in a group of lepromatous leprosy patients without reactions. DESIGN: The initial urine samples were collected from lepromatous leprosy patients when they came with ENL before commencing antireactional therapy and repeat samples were taken after resolution of ENL. Morning urine samples were collected from LL patients without reactions. Nitrites and nitrates in urine were measured using commercially available kit. Mean levels of nitric oxide metabolites of LL patients with ENL and without ENL were compared by student's 't' test. The level during ENL and after resolution was compared by paired 't' test. RESULTS: The nitric oxide metabolites were analyzed in 14 LL patients with ENL and after resolution of ENL and in 5 LL patients without reaction. The level of urinary nitric oxide metabolite is higher in LL patients in ENL reaction compared to LL patients without reaction (P < 0.04). These levels were reduced significantly with resolution of reaction following antireactional therapy (P < 0.004). CONCLUSION: The findings of this study suggested that the NO/NOM excretion is increased in leprosy patients during ENL episodes. With antireactional therapy (steroids) and clinical improvement the levels are reduced.

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.

Prevalence of leprosy in Agra District (U.P.) India from 2001 to 20031.

Leprosy prevalence has reportedly declined all over the world, but six countries, including India, are still endemic for the disease. India alone contributes about 60% to the world's leprosy case load, with the major share from its northern states. The present study done in Agra district was based on a randomly-selected sample of over 10% of the population, spread across 300 villages and 16 urban units of the district. A house-to-house survey was conducted from July 2001 to July 2003 in all the 26 selected panchayats (300 villages), all the 11 block headquarters which have an urban component, and 5 (out of 20) localities in Agra city. A population of 361,321 persons was examined for leprosy. A total of 592 leprosy cases [new and cases yet to complete a full course of multi-drug therapy (M.D.T.)] were found, giving a prevalence rate of 16.4/10,000 population. Although the overall prevalence was found to be similar in both rural and urban areas, there were pockets with high prevalence. More cases were detected in the eastern side of Agra (31.4/10,000 in Fatehabad and 28.5/10,000 in Bah Tahsils). Overall, the multibacillary (MB) leprosy rate was 22.3% and the child leprosy rate 8.4%. Of the 592 cases, 523 (88.3%) were new untreated cases, giving a new case detection rate of 14.5/10,000. The MB rate was 17% (89/523), and the child leprosy rate was 8.4% (44/523) among the new patients. The grade 2 deformity rate was found to be 4.8% (25/523) among these cases. The duration of disease among new cases was 32.3 months as compared to 48.1 months among prevalent (registered) cases (i.e., patients who had been diagnosed earlier and had yet to complete a full course of M.D.T.). The large number of undetected cases found in this survey suggests the need for continued intensive health education campaigns and case detection activities. This study highlights the fact that a large number of leprosy cases go undetected in the present integrated system which is mainly based on voluntary reporting of cases.

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.

Pattern of bacillary clearance in multibacillary leprosy patients with multidrug therapy.

The bacteriological index (BI) of the skin smears is traditionally one of the important parameters of assessment of severity and of progress of leprosy under multidrug therapy. The present study reports on BI clearance among 578 multibacillary treated leprosy patients and the factors that influence this clearance. The patients were treated till smear negativity or for 2 years fixed duration and their skin smears periodically examined every 6 to 12 months till negativity (and even afterwards). We confirm that bacterial clearance is a slow process. The time taken for each log-unit decline in BI is between 13.6 to 24 months probably depending on initial BI level. The rate of smear negativity appears to be dependent on immune competence of the patients as reflected by a rapid BI decline in borderline BT-BB patients vis-à-vis BL-LL lepromatous patients both in the low and high BI group. Patients who had several episodes of ENL, took significantly longer time (63.7 months versus 53.5 months, p<0.0001) to become smear negative than those without ENL.

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 intermettnt steroid administration was observed. This coul 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 non-availability 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), Lieblin et al 1981 and Pasricah & 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

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.

Some epidemiological observations on leprosy in India

This population sample survey conducted in rural and urban areas of the Agra District in India showed an active leprosy caseload of 60.1/10,000 in the rural and 39.1/10,000 in the urban areas against a targeted prevalence of < 1/10,000. The disease appeared to be widespread since almost 65% of the villages or urban pockets surveyed had at least one prevalent case of leprosy. Significantly larger numbers of leprosy patients were found among males, agricultural/manual workers, persons with no formal schooling, individuals living in unkept households with dirty surroundings, and among those living in dark and poorly ventilated houses. The epidemiological significance of this study reveals the endemic nature of leprosy in Agra and suggests the need to intensify and widen case-detection activities to achieve leprosy control.