Stakeholders perspectives on perceived needs and priorities for leprosy control and care, Tamil Nadu, India.

Although leprosy has been declared as eliminated in India, treated patients with persisting disabilities still require care. With the shift from vertical to integrated services, questions remain about case detection and maintaining the quality of patient care. We conducted a qualitative study to clarify the perceived status of elimination, patient care and other aspects of leprosy control from the perspective of various stakeholders. We interviewed leprosy programme managers, Non-governmental organization directors, healthcare providers, patients and community leaders from Kanchipuram district, Tamil Nadu. Consensus endorsed the current approach to integration of leprosy in primary healthcare, but healthcare personnel acknowledged problems from shortage of medicines and failure to fill key positions. Patients were concerned about limited clinic hours, long waits and delayed treatment. Disabled patients indicated how they were troubled by stigmatization of their condition. Programme managers mentioned limited support for needed research and some emphasized the potential threat of emerging drug resistance. Although consensus supports an integrated approach for leprosy services in primary care, the relative priority of different aspects of leprosy control vary among stakeholders. Perspectivist approaches to methodologically sound operational research could guide planning for effective case detection and patient care during the post-elimination era.

Efficacy of single-dose chemotherapy (rifampicin, ofloxacin and minocycline-ROM) in PB leprosy patients with 2 to 5 skin lesions, India: randomised double-blind trial.

UNLABELLED: We conducted randomized double-blind trial for single-dose of Rifampicin, Ofloxacin and Minocycline (ROM) compared to WHO-PB-MDT among paucibacillary (PB) leprosy patients with 2-5 skin lesions. We enrolled 1526 patients from five centres (ROM=762; WHO-PB-MDT=764) and followed them for 36 months posttreatment during 1998-2003. We generated information on clearance of skin lesions and relapse rates per 100 person-years (PY) for all the five centres. At base-line, the patients in the two arms were comparable. Complete clearance of skin lesions was similar (72% vs. 72.1%; p=0.95) in both the arms. Clinical scores declined steadily and equally. Difference in relapse rates was statistically highly significant (ROM=1.13 and WHO-PB-MDT=0.35 per 100 PY; mid-p exact=0.001016). Twenty eight of 38 of these relapses occurred within 18 months. In all, 10 suspected adverse drug reactions were.observed (ROM=2; WHO-PB-MDT=8). We extended the follow-up to 48 months for 1082 of 1526 patients from two programme-based centres. No further relapses occurred. Decline in clinical score was not dependent on age, gender, number of lesions or affected body parts. Single dose ROM, though less effective than the standard WHO-PB-MDT regimen conceptually offers an alternative treatment regimen for PB leprosy patients with 2-5 lesions only when careful follow-up for relapse is possible. Registered at the Clinical Trials Registry of India; REGISTRATION NUMBER: CTRI/2012/05/002645

International open trial of uniform multi-drug therapy regimen for 6 months for all types of leprosy patients: rationale, design and preliminary results.

OBJECTIVE: To describe the rationale, design and preliminary results of an open trial of 6 months uniform multi-drug therapy (U-MDT) for all types of leprosy patients assuming a cumulative relapse rate not exceeding 5% over 5 years of follow-up. METHODS: We intended to recruit 2500 patients each in multi-bacillary (MB) and pauci-bacillary (PB) groups from India (five centres) and China (two centres). Standardized clinical criteria were used to assess skin lesions in the field. RESULTS: A total of 2912 patients enrolled from November 2003 to May 2007 (India, 2746; China, 166). MB patients constituted 39% and 3% had grade 2 disability. During follow-up, 27 patients (0.9%) developed new lesions. Of these, 78% were on account of reactions. Six patients had clinically confirmed relapse. Clofazimine-related skin pigmentation was short-lived and was acceptable to patients. We analysed data for clinical status of skin lesions. About 2.9% of patients were lost to follow-up; 85.9% completed treatment, of whom 19% had inactive skin lesions. PB patients responded better than MB patients (27%vs. 6%; P < 0.001). At the end of the first (n = 2013) and second year (n = 807) of follow-up post-U-MDT, in 49% and 46% patients, lesions were inactive, respectively (59% and 57% in PB, 37% and 28% in MB; P < 0.001). CONCLUSION: U-MDT appears to be promising with respect to clinical status of skin lesions.

Lesional characteristics and histopathology in paucibacillary leprosy patients with 2 or 3 skin lesions: comparison between ROM and PB-MDT regimens.

Paucibacillary (PB) patients form a large segment of newly diagnosed leprosy patients and those who present with only two or three skin lesions could have problems with compliance. With prolonged anti-leprosy drug regimens that last over six months. ROM therapy, a one-dose regimen, offers an attractive alternative in treating such patients. We conducted a longitudinal study of 51 such PB patients, placing them in two groups at random: one receiving the standard PB-MDT regimen, and the other the ROM regimen. Patients were followed up for 2 years, with a comprehensive clinical examination done every six months. 14 patients, 7 in each group, also had their skin biopsies evaluated histopathologically at recruitment, at 6 months and at the end of 2 years. There was a consistent improvement of lesions in both the groups over time. The fall in granuloma fraction and the clearance of the initial bacterial index were seen in the histopathology of both groups. Although the PB-MDT regimen is an effective and robust one, the operational convenience and drug compliance with ROM could make it an acceptable, parallel regimen for PB patients when the disease is localized to 2 or 3 skin lesions.

Trends of case detection and other indicators of leprosy in China during 1985-2002.

OBJECTIVE: To analyze the trends of case detection and other indicators of leprosy in China during 1985-2002. METHODS: Data reported by each province were collected by China National Leprosy Database in Nanjing P.R. China. All data about registered cases were put into computer for analysis. RESULTS: From 1985 to 2002, a total of 49,477 new leprosy cases had been detected. Among them, 69.5% were multibacillary cases and 25.4% had grade 2 disability. The child cases aged below 15 years accounted for 3.74% of total cases. Totally, 5824 cases and 303 cases relapsed after dapsone (DDS) mono-therapy and multidrug therapy (MDT), respectively. Case detection showed a marked reduction from 0.47/100,000 in 1985 to 0.18/100,000 in 1993 although there were several spurts due to operational factors. From 1994, case detection showed no significant decline. The grade 2 disability among new patients decreased from 31.4% in 1985 to 23.4% in 2002. The child case detection rate among new cases fluctuated between 2.70%-3.56% from 1999 to 2002. The incidence of relapse declined after the introduction of DDS mono-therapy. However, it increased after the introduction of MDT. CONCLUSION: China experiences in leprosy control show that it will take a long time with continuing present leprosy control activities to bring down the case detection and other indicators to a very low level even after reaching the elimination goal of leprosy.

Evaluación de Técnicas Serodiagnósticas para la Lepra. Estudio en una población endémica del sur de la India / tab

Para evaluar la utilidad de los antígenos disacárido natural (PGL1) y 35 kDa en determinaciones serológicas de lepra sobre todo para la detección de grupos de alto riesgo para contraer la enfermedad, se llevó a cabo este estudio en una población endémica del sur de la India. De 3.346 casos y sus convivientes y vecinos, se obtuvieron muestras de suero de 2.994 y 2.875 individuos y se cribaron para detectar antígenos frente al PGL1 y 35 kDa respectivamente. Mientras que la positividad total para contactos y casos de lepra era del 3,3% para anticuerpos PGL1, la positividad para el anticuerpo 35 kDa era del 6,3%. La seropositividad para la población contacto era del 2,7% y 5,4% para anticuerpos PGL1 Y 35 kDa, respectivamente. Los pacientes lepromatosos y bordeline lepromatosos presentaron positividades del 35,1% para anticuerpos PGL1 y 45,7% para el 35 kDa. El seguimiento de los contactos reveló que la mayoría de los analizados permanece (>90%9 seronegativos para ambos anticuerpos y la mayoría de nuevos casos se presentaron precisamente en el grupo seronegativo. El ensayo demuestra claramente que las técnicas serológicas específicas no son lo suficientemente sensibles para su aplicación, tanto para el diagnóstico como para identificar individuos en riesgo de contraer lepra en esta población endémica del sur de la India (AU)

In order to evaluate the usefulness of natural disaccharide (PGL1) and 35 kDa antigens based serology in diagnosis of leprosy and in detecting high risk groups for leprosy, this study was conducted in an endemic population in South India. 90%) remained seronegative for both the antibodies and most of the new cases emerged form the seronegative group. The study clearly indicates that specific serological assays are not sensitive enough for application, both for diagnosis and for identifying any individuals at risk for leprosy in the south Indian endemic population (AU)

Trends in case detection influenced by leprosy elimination campaigns in certain areas of China.

LECs were carried out from 1998 to 2000 in eight counties of west China. The number of cases detected during the year of LECs was much higher than that detected by routine methods before the year of the LEC. However, the annual number of cases detected during the year after the LEC showed different patterns. One pattern is that the number of new cases detected in the year after the LEC declined to the level similar to that before the year of the LEC. The second pattern is that the number of new cases detected in the year after the LEC declined steeply to less than that detected before the year of the LEC. Following peak case-detection during the year of the LEC, a gradual decrease in the number of new cases was observed in the subsequent years. The repeat LEC brought a weakly rebounding peak case-detection during the year following the first LEC carried out 3 years earlier. The operational, epidemiological and technical factors influencing the trends of case-detection during the LECs are discussed.

Utility of serodiagnostic tests for leprosy: a study in an endemic population in South India.

In order to evaluate the usefulness of natural disaccharide (PGL1) and 35 kDa antigens based serology in diagnosis of leprosy and in detecting high risk groups for leprosy, this study was conducted in an endemic population in South India. Out of 3346 cases and their households and neighbouring household contacts, serum samples from 2994 and 2875 individuals were screened for antibodies against PGL1 and 35kDa antigens respectively. While the overall positivity for contacts and leprosy cases was 3.3% for PGL1 antibody, the positivity for 35 kDa antibody was 6.3%. The positivity for contact population was 2.7% and 5.4% for PGL1 and 35 kDa antibodies, respectively. Lepromatous and borderline lepromatous patients showed positivity of 35.1% for PGL1 antibody and 45.7% for 35 kDa antibody. Follow-up of contacts showed that the majority (>90%) remained seronegative for both the antibodies and most of the new cases emerged from the seronegative group. The study clearly indicates that specific serological assays are not sensitive enough for application, both for diagnosis and for identifying any individual at risk for leprosy in the south Indian endemic population.

Application of lot quality assurance sampling for leprosy elimination monitoring--examination of some critical factors.

BACKGROUND: The concept of elimination of an infectious disease is different from eradication and in a way from control as well. In disease elimination programmes the desired reduced level of prevalence is set up as the target to be achieved in a practical time frame. Elimination can be considered in the context of national or regional levels. Prevalence levels depend on occurrence of new cases and thus could remain fluctuating. There are no ready pragmatic methods to monitor the progress of leprosy elimination programmes. We therefore tried to explore newer methods to answer these demands. With the lowering of prevalence of leprosy to the desired level of 1 case per 10000 population at the global level, the programme administrators' concern will be shifted to smaller areas e.g. national and sub-national levels. For monitoring this situation, we earlier observed that lot quality assurance sampling (LQAS), a quality control tool in industry was useful in the initially high endemic areas. However, critical factors such as geographical distribution of cases and adoption of cluster sampling design instead of simple random sampling design deserve attention before LQAS could generally be recommended. The present exercise was aimed at validating applicability of LQAS, and adopting these modifications for monitoring leprosy elimination in Tamil Nadu state, which was highly endemic for leprosy. METHODS: A representative sample of 64000 people drawn from eight districts of Tamil Nadu state, India, with maximum allowable number of 25 cases was considered, using LQAS methodology to test whether leprosy prevalence was at or below 7 per 10000 population. Expected number of cases for each district was obtained assuming Poisson distribution. Goodness of fit for the observed and expected cases (closeness of the expected number of cases to those observed) was tested through chi(2). Enhancing factor (design effect) for sample size was obtained by computing the intraclass correlation. RESULTS: The survey actually covered a population of 62157 individuals, of whom 56469 (90.8%) were examined. Ninety-six cases were detected and this number far exceeded the critical value of 25. The number of cases for each district and the number of cases in the entire surveyed area both followed Poisson distribution. The intraclass correlation coefficients were close to zero and the design effect was observed to be close to one. CONCLUSIONS: Based on the LQAS exercises leprosy prevalence in the state of Tamil Nadu in India was above 7 per 10000. LQAS method using clusters was validated for monitoring leprosy elimination in high endemic areas. Use of cluster sampling makes this method further useful as a rapid assessment procedure. This method needs to be tested for its applicability in moderate and low endemic areas, where the sample size may need increasing. It is further possible to consider LQAS as a monitoring tool for elimination programmes with respect to other disease conditions.

Lot quality assurance sampling (LQAS) for monitoring leprosy elimination in an endemic district in Tamilnadu.

This paper examines whether the health administration can use lot quality assurance sampling (LQAS) for identifying high prevalence areas for leprosy for initiating necessary corrective measures. The null hypothesis was that leprosy prevalence in the district was at or above ten per 10,000 and the alternative hypothesis was that it was at or below five per 10,000. A total of 25,500 individuals were to be examined with 17 as an acceptable maximum number of cases (critical value). Two-stage cluster sample design was adopted. The sample size need not be escalated as the estimated design effect was 1. During the first phase, the survey covered a population of 4,837 individuals out of whom 4,329 (89.5%) were examined. Thirty-five cases were detected and this number far exceeded the critical value. It was concluded that leprosy prevalence in the district should be regarded as having prevalence of more than ten per 10,000 and further examination of the population in the sample was discontinued. LQAS may be used as a tool by which one can identify high prevalence districts and target them for necessary strengthening of the programme. It may also be considered for certifying elimination achievement for a given area.

Modelling epidemiology of leprosy.

A simulation model for leprosy transmission and control has been developed with specific objectives. Several sensitivity experiments have been carried out by altering the various inputs based on empirical data combined with intelligent guessing. The outputs generated through these exercises were on the expected lines. While incremental exercises would improve the model, it can be used even at the existing stage as a tool for programme managers.

SIMLEP: a simulation model for leprosy transmission and control.

SIMLEP is a computer program for modeling the transmission and control of leprosy which can be used to project epidemiologic trends over time, producing output on indicators such as prevalence, incidence and case-detection rates of leprosy. In SIMLEP, health states have been defined that represent immunologic conditions and stages of leprosy infection and disease. Three types of interventions are incorporated: vaccination, case detection and chemotherapy treatment. Uncertainties about leprosy have led to a flexible design in which the user chooses which of many aspects should be included in the model. These aspects include natural immunity, asymptomatic infection, type distribution of new cases, delay between onset of disease and start of chemotherapy, and mechanisms for leprosy transmission. An example run illustrates input and output of the program. The output produced by SIMLEP can be readily compared with observed data, which allows for validation studies. The support that SIMLEP can give to health policy research and actual decision making will depend upon the extent of validation that has been achieved. SIMLEP can be used to improve the understanding of observed leprosy trends, for example, in relation to early detection campaigns and the use of multidrug therapy, by exploring which combinations of assumptions can explain these trends. In addition, SIMLEP allows for scenario analysis in which the effects of control strategies combining different interventions can be simulated and evaluated.

Lot quality assurance sampling (LQAS) for monitoring a leprosy elimination program.

In a statistical sense, prevalences of leprosy in different geographical areas can be called very low or rare. Conventional survey methods to monitor leprosy control programs, therefore, need large sample sizes, are expensive, and are time-consuming. Further, with the lowering of prevalence to the near-desired target level, 1 case per 10,000 population at national or subnational levels, the program administrator's concern will be shifted to smaller areas, e.g., districts, for assessment and, if needed, for necessary interventions. In this paper, Lot Quality Assurance Sampling (LQAS), a quality control tool in industry, is proposed to identify districts/regions having a prevalence of leprosy at or above a certain target level, e.g., 1 in 10,000. This technique can also be considered for identifying districts/regions at or below the target level of 1 per 10,000, i.e., areas where the elimination level is attained. For simulating various situations and strategies, a hypothetical computerized population of 10 million persons was created. This population mimics the actual population in terms of the empirical information on rural/urban distributions and the distribution of households by size for the state of Tamil Nadu, India. Various levels with respect to leprosy prevalence are created using this population. The distribution of the number of cases in the population was expected to follow the Poisson process, and this was also confirmed by examination. Sample sizes and corresponding critical values were computed using Poisson approximation. Initially, villages/towns are selected from the population and from each selected village/town households are selected using systematic sampling. Households instead of individuals are used as sampling units. This sampling procedure was simulated 1000 times in the computer from the base population. The results in four different prevalence situations meet the required limits of Type I error of 5% and 90% Power. It is concluded that after validation under field conditions, this method can be considered for a rapid assessment of the leprosy situation.