Correction: The role of perceptions and knowledge of leprosy in the elimination of leprosy: A baseline study in Fatehpur district, northern India.

[This corrects the article DOI: 10.1371/journal.pntd.0007302.].

Prolaxis post-exposición para lepra con dosis única de rifampicina: manual para su implementación / Post-exposure prolaxis for leprosy with a single dose of rifampicin: a manual for its implementation

Objetivo: La profilaxis post-exposición de la lepra con dosis única de rifampicina (SDR-PEP) ha demostrado ser efectiva y aplicable y está recomendada por la OMS desde 2018. Esta caja de herramientas SDR-PEP se desarrolló a través de la experiencia de la profilaxis lepra post-eliminación (LPEP). Se ha diseñado para facilitar y estandarizar la implementación del seguimiento de contactos y la administración SDR-PEP en regiones y países que iniciaron la intervención. Resultados: Se desarrollaron cuatro instrumentos, incorporando la evidencia existente actual para SDR-PEP y los métodos y enseñanzas del proyecto LPEP en ocho países. (1) El conjunto de diapositivas Powerpoint política/apoyo que ayudarán a los programadores sobre la evidencia, practicabilidad y recursos necesarios para SDR-PEP, (2) La colección de diapositivas PowerPoint sobre formación e implementación en el campo para formar al personal implicado en el seguimiento de contactos y PEP con SDR, (3) manual genérico de campo SDR-PEP que puede ser usado para formar un protocolo específico de campo para el seguimiento de contactos y SDR-PEP como referencia para el personal directamente implicado. Finalmente, (4) el manual director SDR-PEP, que resume los distintos componentes de la caja de herramientas y contiene las instrucciones para su uso. Conclusión: En respuesta al interés manifestado por varios países de implementar el seguimiento de contactos de lepra con PEP con SDR, con las recomendaciones OMS sobre SDR-PEP, esta caja de herramientas basada en la evidencia concreta pero flexible, ha sido diseñada para servir a los directores de programas nacionales de lepra con un medio práctico para trasladar los planteamientos a la práctica. Está disponible gratuitamente en la página de Infolep y actualizada constantemente: https://www.leprosy-information.org/keytopic/leprosy-post-exposure-prophylaxis-lpep-programme(AU).

Objective: Leprosy post-exposure prophylaxis with single-dose rifampicin (SDRPEP) has proven effective and feasible, and is recommended by WHO since 2018. This SDR-PEP toolkit was developed through the experience of the leprosy post-exposure prophylaxis (LPEP) programme. It has been designed to facilitate and standardise the implementation of contact tracing and SDR-PEP administration in regions and countries that start the intervention. Results: Four tools were developed, incorporating the current evidence for SDRPEP and the methods and learnings from the LPEP project in eight countries. (1) the SDR-PEP policy/advocacy PowerPoint slide deck which will help to inform policy makers about the evidence, practicalities and resources needed for SDR-PEP, (2) the SDR-PEP field implementation training PowerPoint slide deck to be used to train front line staff to implement contact tracing and PEP with SDR, (3) the SDR-PEP generic field guide which can be used as a basis to create a location specific field protocol for contact tracing and SDR-PEP serving as a reference for frontline field staff. Finally, (4) the SDR-PEP toolkit guide, summarising the different components of the toolkit and providing instructions on its optimal use. Conclusion: In response to interest expressed by countries to implement contact tracing and leprosy PEP with SDR in the light of the WHO recommendation of SDRPEP, this evidence-based, concrete yet flexible toolkit has been designed to serve national leprosy programme managers and support them with the practical means to translate policy into practice. The toolkit is freely accessible on the Infolep homepages and updated as required: https://www.leprosy-information.org/keytopic/leprosy-postexposure-prophylaxis-lpep-programme(AU).

The role of perceptions and knowledge of leprosy in the elimination of leprosy: A baseline study in Fatehpur district, northern India.

BACKGROUND: With the introduction of new interventions to prevent leprosy, such as post-exposure prophylaxis (PEP) given to contacts of leprosy patients, it is necessary to update our understanding of knowledge and perception of leprosy among the populations where these interventions will be introduced, in order to tailor communication optimally to the current situation. This study is a baseline study of the PEP++ project and aimed to assess the knowledge, attitudes and practices regarding leprosy in Fatehpur, India. METHODOLOGY: The study used a community-based cross-sectional design with a mixed-methods approach. We assessed knowledge, attitudes, and practices with the KAP measure, and stigma with the Explanatory Model Interview Catalogue community stigma scale (EMIC-CSS) and the Social Distance Scale (SDS). In addition, semi-structured interviews and focus group discussions were conducted with all participant groups. The quantitative data were analysed using stepwise multivariate regression. The qualitative data were analysed using open, inductive coding and content analysis. FINDINGS: A total of 446 participants were included in the study: 100 persons affected by leprosy, 111 close contacts, 185 community members and 50 health care workers. In addition, 24 in-depth interviews were conducted and 35 people were included in focus group discussions. 12.5% of the participants had adequate knowledge of leprosy, while 22% had poor knowledge. Knowledge on cause (answered correctly by 10% of the participants), mode of transmission (5%) and symptoms of leprosy (16%) was especially poor. The mean EMIC-CSS score was 15.3 (95%CI 14.6-16.0) and mean SDS score 7.2 (95%CI 6.6-7.8). Better knowledge of leprosy was associated with lower levels of social distance towards persons affected by leprosy. CONCLUSION: This study revealed poor knowledge regarding leprosy and high levels of stigma and fear and desire to keep social distance towards persons affected by leprosy. Community education that takes cultural beliefs, knowledge gaps and fears into consideration could improve knowledge, reduce misconceptions and positively influence the perception of leprosy.

Genus Psoralea: A review of the traditional and modern uses, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Psoralea (Fabaceae) harbours 105 accepted species that are extensively used by local peoples and medicinal practitioners of China, India, and other countries for treatment of tooth decay, psoriasis, leucoderma, leprosy, kidney problems, tuberculosis, indigestion, constipation and impotence. Presently, pharmacological research reports are available on only few species namely Bituminaria bituminosa (Syn: P. bituminosa), P. canescens, P. corylifolia, P. esculenta, P. plicata and P. glandulosa which are valued for their chemical constituents and traditional uses. AIM OF THE REVIEW: This review article provides explicit information on traditional uses, phytochemistry, and pharmacological activities of selected Psoralea species. The possible trends and perspectives for future research on these plants are also discussed. MATERIALS AND METHODS: An extensive and systematic review of the extant literature was carried out, and the data under various sections were identified using a computerized bibliographic search via the PubMed, Web of Science and Google Scholar, CAB Abstracts, MEDLINE, EMBASE, INMEDPLAN, NATTS as well as several websites. KEY FINDINGS: A total of 291 bioactive compounds from 06 species of genus Psoralea have been isolated and characterized. However, P. bituminosa alone possess nearly 150 compounds. These bioactive compounds belong to different chemical classes, including flavonoids, coumarins, furanocoumarins, chalcones, quinines, terpenoids and some others due to which these species exhibit significant anti-oxidant, anti-bacterial, anti-fungal, anti-viral, anti-helmintic, anti-diabetic, diuretic, hepatoprotective, anti-cancer and anti-tumor activities. P. corylifolia L. (Babchi), a Chinese traditional medicinal plant has been used in traditional medicine for many decades for its healing properties against numerous skin diseases such as leprosy, psoriasis and leucoderma. CONCLUSIONS: The in vitro studies and in vivo models have provided a simple bio-scientific justification for various ethnopharmacological uses of Psoralea species. From the toxicological perspective, the root, leaf, and seed extracts and their preparations have been proven to be safe when consumed in the recommended doses. But, meticulous studies on the pharmaceutical standardization, mode of action of the active constituents, and sustainable conservation of Psoralea species are needed, to meet the growing demands of the pharmaceutical industries, and to fully exploit their preventive and therapeutic potentials.

Programa post-exposición a la profilaxis de la Lepra (LPEP): Actualización y análisis interno / No disponible

Se requieren nuevos planteamientos para incrementar el control de la lepra, disminuir el número de personas afectadas y cortar la transmisión. Para conseguir este objetivo las mejores soluciones son la detección precoz. El cribaje de contactos y la quimioprofilaxis. El Programa Profilaxis Post-exposición a la Lepra (LPEP) ayuda a demostrar la viabilidad de integrar el rastreo de contactos y dosis única de rifampicina (SDR) en las actividades rutinarias de control de la enfermedad. El programa LPEP está implementado entre los programas de control de la lepra de Brasil, Camboya, India, Indonesia, Myanmar, Nepal, Sri Lanka y Tanzania. Se centra en tres objetivos: rastro de contactos de nuevos pacientes diagnosticados de lepra, cribaje de contactos y administración de SDR a los contactos seleccionados. Las adaptaciones de protocolos países-específicos se refieren a la definición de contacto, edad mínima para SDR y personal implicado. La calidad de la evidencia se mantiene mediante coordinación central, documentación detallada y supervisión. Ya se han completado alrededor de 2 años de trabajo de campo en siete países en julio de 2017. Los 5,941 pacientes índice registrados (89·4% de los registrados) han identificado un total de 123,311 contactos, de los cuales el 99·1% ha sido rastreado y cribado. De entre ellos, se identificaron 406 nuevos pacientes de lepra (329/100,000) y a 10,883 (8·9%) no se les administró SDR por diversos motivos. También 785 contactos (6·7%) rehusó tomar la profilaxis con SDR. En total, se administró SDR al 89·0% de los contactos registrados. La profilaxis post-exposición con SDR es segura; se puede integrar en los programas rutinarios de control de la lepra y es generalmente bien aceptada por el paciente índice, sus contactos y el personal sanitario. El programa también consigue estimular los programas locales de control de la lepra

Innovative approaches are required to further enhance leprosy control, reduce the number of people developing leprosy, and curb transmission. Early case detection, contact screening, and chemoprophylaxis currently is the most promising approach to achieve this goal. The Leprosy Post-Exposure Prophylaxis (LPEP) programme generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities in different settings. The LPEP programme is implemented within the leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Focus is on three key interventions: tracing the contacts of newly diagnosed leprosy patients; screening the contacts for leprosy; and administering SDR to eligible contacts. Country-specific protocol adaptations refer to contact definition, minimal age for SDR, and staff involved. Central coordination, detailed documentation and rigorous supervision ensure quality evidence. Around 2 years of field work had been completed in seven countries by July 2017. The 5,941 enrolled index patients (89·4% of the registered) identified a total of 123,311 contacts, of which 99·1% were traced and screened. Among them, 406 new leprosy patients were identified (329/100,000), and 10,883 (8·9%) were excluded from SDR for various reasons. Also, 785 contacts (0·7%) refused the prophylactic treatment with SDR. Overall, SDR was administered to 89·0% of the listed contacts. Post-exposure prophylaxis with SDR is safe; can be integrated into the routines of different leprosy control programmes; and is generally well accepted by index patients, their contacts and the health workforce. The programme has also invigorated local leprosy control

Incidence of leprosy in Firozabad district (Uttar Pradesh).

OBJECTIVE: To assess incidence of leprosy in Firozabad District (U.P.). MATERIALS AND METHODS: A random sample of 148,061 population was covered by this second survey, spread over 259 units (230 rural/29 urban). The survey was conducted between March 2011 and November 2012. Clinically confirmed cases detected in known disease-free population were labeled as incident cases and treated. RESULTS: The overall incidence rate of leprosy was found to be 3.4 per 10,000 person years; In healthy contacts it was 3.1, in paucibacillary contacts 29.7 while it was 89.3 in multibacillary contacts. The differences in incidence rate of these three groups were significant (P < 0.001). Incidence rate was significantly higher by age; 1.1 in persons <15 years to 8.0 in those >44 years of age, and in high endemicity areas with three or more cases. In terms of incidence rate ratio (95% confidence interval), the incidence for ages 15-24 years was 3.2 times significantly higher than for those under 15 years, 5.3 times (4.3-6.5) in ages 30-44 years and 7.0 times (5.6-8.7) for age ≥45 years. Incidence rate ratio was also significantly higher in paucibacillary contacts, by 9.5 times (7.0-13.0) and 27.7 times (18.8-40.6) in multibacillary contacts, as compared to healthy controls. Incidence rate ratio (95% confidence interval) was significantly higher by 2.9 times (2.4-3.5) in areas with endemicity status of 3 to 5 cases and by 2.0 times (1.6-2.5) in areas with >5 cases as compared to areas with no endemicity. It was 2.4 times more (1.6-3.5) in Narkhi, 2.4 times higher (1.7-3.5) in Tundla and 3.0 times higher (2.1-4.5) in Aravon blocks than in Aeka block of the district. Incidence rate was also found to be significantly higher (3.7) among females, 1.3 times higher (1.1-1.5) than in males (2.9). Incidence rate ratio (95% confidence interval) was also 2.5 times higher (1.2-5.1) among persons having reported disease of greater than 4 years in comparison to 1.5 in persons having disease for 2 to 3 years. LIMITATIONS OF STUDY: None to the best of our knowledge. CONCLUSION: The present study suggests that incidence rate of leprosy is significantly higher among persons of above 15 years, in females, among contacts of paucibacillary/multibacillary disease, in areas where >3 leprosy cases were found and in Tundla, Narkhi and Aravon blocks in Firozabad district.

The Leprosy Post-Exposure Prophylaxis (LPEP) programme: update and interim analysis.

Innovative approaches are required to further enhance leprosy control, reduce the number of people developing leprosy, and curb transmission. Early case detection, contact screening, and chemoprophylaxis currently is the most promising approach to achieve this goal. The Leprosy Post-Exposure Prophylaxis (LPEP) programme generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities in different settings. The LPEP programme is implemented within the leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Focus is on three key interventions: tracing the contacts of newly diagnosed leprosy patients; screening the contacts for leprosy; and administering SDR to eligible contacts. Country-specific protocol adaptations refer to contact definition, minimal age for SDR, and staff involved. Central coordination, detailed documentation and rigorous supervision ensure quality evidence. Around 2 years of field work had been completed in seven countries by July 2017. The 5,941 enrolled index patients (89·4% of the registered) identified a total of 123,311 contacts, of which 99·1% were traced and screened. Among them, 406 new leprosy patients were identified (329/100,000), and 10,883 (8·9%) were excluded from SDR for various reasons. Also, 785 contacts (0·7%) refused the prophylactic treatment with SDR. Overall, SDR was administered to 89·0% of the listed contacts. Post-exposure prophylaxis with SDR is safe; can be integrated into the routines of different leprosy control programmes; and is generally well accepted by index patients, their contacts and the health workforce. The programme has also invigorated local leprosy control.

Mycobacterial tlyA gene product is localized to the cell-wall without signal sequence.

The mycobacterial tlyA gene product, Rv1694 (MtbTlyA), has been annotated as "hemolysin" which was re-annotated as 2'-O rRNA methyl transferase. In order to function as a hemolysin, it must reach the extracellular milieu with the help of signal sequence(s) and/or transmembrane segment(s). However, the MtbTlyA neither has classical signals sequences that signify general/Sec/Tat pathways nor transmembrane segments. Interestingly, the tlyA gene appears to be restricted to pathogenic strains such as H37Rv, M. marinum, M. leprae, than M. smegmatis, M. vaccae, M. kansasii etc., which highlights the need for a detailed investigation to understand its functions. In this study, we have provided several evidences which highlight the presence of TlyA on the surface of M. marinum (native host) and upon expression in M. smegmatis (surrogate host) and E. coli (heterologous host). The TlyA was visualized at the bacterial-surface by confocal microscopy and accessible to Proteinase K. In addition, sub-cellular fractionation has revealed the presence of TlyA in the membrane fractions and this sequestration is not dependent on TatA, TatC or SecA2 pathways. As a consequence of expression, the recombinant bacteria exhibit distinct hemolysis. Interestingly, the MtbTlyA was also detected in both membrane vesicles secreted by M. smegmatis and outer membrane vesicles secreted by E. coli. Our experimental evidences unambiguously confirm that the mycobacterial TlyA can reach the extra cellular milieu without any signal sequence. Hence, the localization of TlyA class of proteins at the bacterial surface may highlight the existence of non-classical bacterial secretion mechanisms.

A randomized controlled trial to compare cure and relapse rate of paucibacillary multidrug therapy with monthly rifampicin, ofloxacin, and minocycline among paucibacillary leprosy patients in Agra District, India.

OBJECTIVES: To study cure rate and relapse rate of standard World Health Organization paucibacillary multidrug therapy (PB-MDT) with monthly rifampicin, ofloxacin, and minocycline for six months (ROM-6) among paucibacillary leprosy patients. METHODS: A total of 268 patients, detected during active search in Agra district during 2001-2004, who had paucibacillary (PB) leprosy having 1-5 skin lesions and/or one nerve thickening/tenderness, were allocated, using random number tables, to two treatment groups; PB-MDT and ROM-6. On the first day of the month, dose of PB-MDT and of the ROM were given under supervision for 6 months. After completion of drug therapy, patients were followed every 6 months for first 5 years and later annually for next 3 years for monitoring disease status, cure rates, reactions and relapses. Cηi σθuαρε test was used to compare relapse rates. RESULTS: The cure rate at 2 years was 99% in ROM-6 and 97.0% in PB-MDT group, of those who completed treatment and the difference was statistically not significant. At 5 years, only 88 patients in PB-MDT group and 90 patients in ROM-6 group could be followed; all were observed to be cured. However, during the period of 5-8 years, 3 of 67 patients in PB-MDT group and 1 of 73 in ROM-6 group were observed to have relapsed. In all, 10 relapses were noted (3 in ROM-6 and 7 in PB-MDT group) giving a relapse rate of 1.10/100 person years in PB-MDT and 0.435/100 person years in ROM groups (P = 0.053 ; statistically not significant). Of the 10 relapses, 5 occurred within 5 years (3 in PB-MDT group and 2 in ROM-6), 4 during 5-8 years (3 in PB-MDT and 1 in ROM-6), and 1 occurred in MDT group after 8 years. LIMITATION: A number of patients were lost to follow up after release from treatment and thus actual number of relapses in the study could not be assessed. Additionally, diagnosis was purely clinical and histology could not be done for reasons related to functional difficulties in the field. CONCLUSION: The study shows that PB-MDT and ROM-6 have almost similar acceptability, cure rate and relapse rate.

WHO multidrug therapy for leprosy: epidemiology of default in treatment in Agra district, Uttar Pradesh, India.

AIM: To study the magnitude of default, time of default, its causes, and final clinical outcome. METHODS: Data collected in active surveys in Agra is analyzed. Patients were given treatment after medical confirmation and were followed up. The treatment default and other clinical outcomes were recorded. RESULTS: Patients who defaulted have comparable demographic characteristics. However, among defaulters more women (62.7% in PB, 42.6% in MB) were seen than those in treatment completers (PB 52.7% and MB 35.9%). Nerve involvement was high in treatment completers: 45.7% in PB and 91.3% in MB leprosy. Overall default rate was lower (14.8%) in ROM than (28.8%) in standard MDT for PB leprosy (χ 1 (2) = 11.6, P = 0.001) and also for MB leprosy: 9.1% in ROM compared to 34.5% in MDT (χ 1 (2) = 6.0, P = 0.015). Default rate was not different (28.8% versus 34.5%, P > 0.05) in both types of leprosy given MDT. Most patients defaulted at early stage of treatment and mainly due to manageable side effects. CONCLUSION: The default in standard MDT both for PB and MB leprosy was observed to be significantly higher than in ROM treatment. Most defaults occurred at early stage of treatment and major contribution of default is due to side effects like drowsiness, weakness, vomiting, diarrhea, and so forth, related to poor general health. Although about half of the defaulters were observed to be cured 2.2% in PB-MDT and 10.9% of MB-MDT developed disability. This is an issue due to default. Attempts are needed to increase treatment compliance. The use of specially designed disease related health education along with easily administered drug regimens may help to reduce default.

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.

Studies on xylitol production by metabolic pathway engineered Debaryomyces hansenii.

Debaryomyces hansenii is one of the most promising natural xylitol producers. As the conversion of xylitol to xylulose mediated by NAD(+) cofactor dependent xylitol dehydrogenase (XDH) reduces its xylitol yield, xylitol dehydrogenase gene (DhXDH)-disrupted mutant of D. hansenii having potential for xylose assimilating pathway stopping at xylitol, was used to study the effects of co-substrates, xylose and oxygen availability on xylitol production. Compared to low cell growth and xylitol production in cultivation medium containing xylose as the only substrate, XDH disrupted mutants grown on glycerol as co-substrate accumulated 2.5-fold increased xylitol concentration over those cells grown on glucose as co-substrate. The oxygen availability, in terms of volumetric oxygen transfer coefficient, kLa (23.86-87.96 h(-1)), affected both xylitol productivity and yield, though the effect is more pronounced on the former. The addition of extra xylose at different phases of xylitol fermentation did not enhance xylitol productivity under experimental conditions.

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.

Six months fixed duration multidrug therapy in paucibacillary leprosy: risk of relapse and disability in Agra PB cohort study.

BACKGROUND: Many studies have focused on multidrug therapy (MDT) for multibacillary (MB) leprosy and rarely on long-term outcome of paucibacillary (PB) leprosy having recommendation of therapy for 6 months fixed duration therapy for PB patients. Studies on measuring risk of disability are rare. The present study is to assess the cure; default, relapse and disability in a prospective cohort of PB leprosy during follow-up of >4 years after treatment. DESIGN: Prospective. SETTING: Primary in our field area of Agra District. PARTICIPANTS: 920 PB leprosy patients entered the study, 621 completed treatment, 599 followed finally including 271 males, no ethnic differentiation, patients of all age groups except for children below 5 years and old persons above 70 years were not included. TREATMENT: 6 months fixed duration MDT as recommended by WHO. PRIMARY AND SECONDARY OUTCOMES: Treatment completion, cure, relapse and development of disability based on clinical assessment by well-experienced doctors. STATISTICAL METHODS: Data have been analysed using SPSS software, risk is computed as incidence per 100 person-years (PY) and test of significance used. RESULTS: Study reports 91% cure rate. Incidence of relapse was 1.3/100 PY with no significant variation by age, sex, delay in detection, patches and nerves. Crude incidence of disability was 2.2% and varied significantly by age and nerve thickening but not by sex, number of patches, nerves and delay in treatment. Incidence of disability was 0.50/100 PY in treatment completed and 0.43 among defaulters. CONCLUSION: The study concludes that relapses do occur after MDT treatment but at the level of 1-2%, incidence of disability remains low (<1/100 PY) in PB leprosy. Low incidence of relapse and disability suggests that 6 months therapy is quite effective. However, further improvement may help to improve its efficacy. Longer follow-up may add to efficacy measures.

Risk of developing disability in pre and post-multidrug therapy treatment among multibacillary leprosy: Agra MB Cohort study.

OBJECTIVES: If leprosy is a public health problem, it is due to the disabilities it causes. Surprisingly little is known about the risk of disabilities. Even now, mainly cross-sectional studies report disability prevalence. The present study aims to report the risk of disability in pre and post-WHO multidrug therapy (MDT) in multibacillary leprosy patients and to assess the extent of the incidence of disability. METHODS: The study design is prospective and the setting is an institutional field area. Patients were detected during 2001-6 field surveys. Of the 289 multibacillary patients, 146 completed the study. Both sexes were involved. The primary outcome planned was to study cure of disease, relapses and disability in patients receiving MDT. The secondary outcome was to measure reaction and default. Assessment was done clinically. Data have been analysed using SPSS software, logistic, survival analysis was performed and the χ(2) test of significance was used. RESULTS: An important risk factor was found to be three or more nerves involved with odds of 3.73 (1.24-11.2), and delay in treatment; 2.27 (1.04-4.96) at the pre-MDT stage and three or more nerves involved with odds of 2.81 (1.0-7.9) at the post-MDT stage. The incidence of disability was found to be 2.74/100 person-years; 2.69 in the MDT arm and 2.84 in defaulters, with slightly higher disability among early defaulters (3.08) than among late defaulters (2.30). The study suggests that the incidence of disability could be slightly higher if treatment is not completed. CONCLUSION: Early treatment for leprosy is a must for reducing the risk of disability, and treatment delay would increase the risk of disability. It is important to note that the incidence of disability between defaulters and those completing treatment was not found to be significantly different.

A randomised controlled trial assessing the effect of adding clarithromycin to rifampicin, ofloxacin and minocycline in the treatment of single lesion paucibacillary leprosy in Agra District, India.

AIM: To assess if there is any additional short and long-term effect of adding clarithromycin to rifampicin, ofloxacin and minocycline (ROM), the combination here after called C-ROM, in treating single lesion PB leprosy detected in the field. METHODS: 300 patients, detected on active search in Agra district, who had single lesion leprosy but no nerve thickening, were randomly allocated (using random number table) to two treatment groups, 151 to ROM and 149 to C-ROM. All th patients were given single dose of ROM or C-ROM and followed up every 6 months for disease status, cure rate, reaction and relapse. Survival analysis was used to compare relapse rate. RESULTS: The cure rate at 2 years was 93.1% in ROM and 91.4% in C-ROM group. By this time three relapses had occurred in the ROM group while two patients were found to have relapsed in the C-ROM group. Thus, there was no statistical difference in relapse rates (2.1% vs. 1.41%, P = 0.287) in the two groups. Long term observations over 3-5 years revealed nine relapses (five in ROM, four in C-ROM) giving relapse rate of 1.05/100 Person years in ROM and 0.90/100 person years in C-ROM group--again no significant difference was observed (P = 0.87). CONCLUSION: The study shows that addition of clarithromycin to ROM does not significantly improve the efficacy as measured in terms of cure rates and relapse rates in single skin lesion leprosy patients.