The long-term effect of current and new interventions on the new case detection of leprosy: a modeling study.

BACKGROUND: Although the number of newly detected leprosy cases has decreased globally, a quarter of a million new cases are detected annually and eradication remains far away. Current options for leprosy prevention are contact tracing and BCG vaccination of infants. Future options may include chemoprophylaxis and early diagnosis of subclinical infections. This study compared the predicted trends in leprosy case detection of future intervention strategies. METHODS: Seven leprosy intervention scenarios were investigated with a microsimulation model (SIMCOLEP) to predict future leprosy trends. The baseline scenario consisted of passive case detection, multidrug therapy, contact tracing, and BCG vaccination of infants. The other six scenarios were modifications of the baseline, as follows: no contact tracing; with chemoprophylaxis; with early diagnosis of subclinical infections; replacement of the BCG vaccine with a new tuberculosis vaccine ineffective against Mycobacterium leprae ("no BCG"); no BCG with chemoprophylaxis; and no BCG with early diagnosis. FINDINGS: Without contact tracing, the model predicted an initial drop in the new case detection rate due to a delay in detecting clinical cases among contacts. Eventually, this scenario would lead to new case detection rates higher than the baseline program. Both chemoprophylaxis and early diagnosis would prevent new cases due to a reduction of the infectious period of subclinical cases by detection and cure of these cases. Also, replacing BCG would increase the new case detection rate of leprosy, but this effect could be offset with either chemoprophylaxis or early diagnosis. CONCLUSIONS: This study showed that the leprosy incidence would be reduced substantially by good BCG vaccine coverage and the combined strategies of contact tracing, early diagnosis, and treatment of infection and/or chemoprophylaxis among household contacts. To effectively interrupt the transmission of M. leprae, it is crucial to continue developing immuno- and chemoprophylaxis strategies and an effective test for diagnosing subclinical infections.

The impact of leprosy control on the transmission of M. leprae: is elimination being attained?

In 1991 the World Health Assembly decided to 'eliminate leprosy as a public health problem' by the year 2000. Elimination was defined as reducing the global prevalence of the disease to less than 1 case per 10,000. In 2000 the World Health Organization (WHO) announced that elimination was reached globally. Conventionally control of disease is defined as the reduction of disease burden to a locally acceptable level. Elimination of disease is defined as the reduction to zero of the incidence in a defined geographical area, and eradication is defined as the permanent reduction to zero of the worldwide incidence of infection caused by a specific agent. In leprosy however, WHO limited elimination to control instead of transmission, by using prevalence instead of incidence of disease. Leprosy statistics usually report on prevalence and new case detection. Prevalence is linked to length of treatment, which has changed over time. Trends in new case detection rates only reflect trends in incidence rates when no changes occur in case detection, but in the past 25 years case detection in leprosy has been determined strongly by operational factors. For the leprosy elimination strategy it was assumed that MDT would reduce transmission of M. leprae, but there is no convincing evidence for this. Data for evaluating the impact of MDT on transmission are not readily available because leprosy has a long incubation period. Also declines in case detection may have other causes, such as BCG vaccination. Mathematical modelling of the transmission and control of leprosy showed that the elimination strategy reduces transmission slowly, with a predicted annual decline in incidence ranging from 2% to 12%. Early case finding was the key factor to attain this decline. Future projections of the global leprosy burden indicated that 5 million new cases would arise between 2000 and 2020, and that in 2020 there would be 1 million people with WHO grade 2 disability. It is concluded that substantial progress has been made to control leprosy, but when elimination of disease is defined as the reduction to zero of the incidence, leprosy is definitely not eliminated. To attain elimination of leprosy it is necessary to find effective interventions to interrupt transmission of M. leprae and practical diagnostic tools to detect levels of infection that can lead to transmission. This requires extensive research in the areas of epidemiology and microbiology.

The future incidence of leprosy: a scenario analysis.

OBJECTIVE: To investigate the impact of the current strategy for the elimination of leprosy on its incidence and to assess the consequences of failure to sustain this strategy. METHODS: Scenarios for assessing the impact of the elimination strategy were implemented in a computer simulation program. The scenarios reflected the assumptions made regarding contagiousness, transmission and bacille Calmette-Guerin (BCG) vaccination. The trend in case detection rate for the main countries in which leprosy was endemic during 1985-98 was fitted, and incidence up to 2020 was projected. FINDINGS: Owing to the gradual shortening of delays in detection up to 1998, and because of the low relapse rate that occurs with multidrug treatment MDT, incidence is predicted to decrease beyond 2000 in all scenarios. The annual decline was a few per cent higher when favourable assumptions were made about protection and coverage of BCG vaccination. Overall, the predicted annual decline in incidences ranged from 2% to 12%. CONCLUSION: The elimination strategy reduces transmission, but the decline may be slow. Relaxation of control after 2005 is unjustified given the uncertainty about the rate of decline and the adverse effects of longer delays in detection. A long-term strategy for leprosy control should be adopted.

Trends in leprosy case detection worldwide since 1985.

Trends in case detection and case detection rate (CDR) since 1985 are described at regional and national levels. Annual case detection by WHO Region was available for 1994-2000. Using different sources, complete time series for case detection were constructed for 1985-1998 for a group of 33 endemic countries cumulatively (top 33), and for 14 individual countries (top 14). Population statistics were used to derive CDRs. India contributed 79% to global case detection in 1998. Africa, the Americas and South-East Asia each contributed about 30% when India is excluded. During 1994-2000, case detection did not decrease in these three WHO Regions. The 33 countries contributed 99% and 98% to global case detection in 1994 and 1998, respectively. Cumulative case detection for the top 33 minus India gradually increased, overall almost doubling. The contribution of the top 14 to case detection of the top 33 hardly changed over time, equalling 96% in 1998 (81% when India is excluded). In terms of annual case detection, Brazil was always ranked second after India; it accounted for 27% of 1998 case detection in the top 33 except India. In 1998, seven of the top 14 countries--including India and Brazil--had CDRs above 2 per 10,000. The CDR did not exceed 1 per 10,000 for the other half. Decreasing tendencies in CDR, either for the whole period or in the 1990s, are observed for four of the top 14 countries (Guinea and three Western Pacific countries: China, Vietnam and the Philippines). In conclusion, there is no general decline in case detection to date, and several important countries still have high CDRs. Prevalence is an irrelevant indicator for monitoring epidemiological changes in leprosy. Trends in the transmission and incidence of leprosy are still completely unclear, necessitating further research. The target to eliminate leprosy as a public health problem, defined as a prevalence of less than 1 per 10,000, is therefore also an inadequate yardstick for decision making on leprosy control.

The future incidence of leprosy: a scenario analysis

Objective: To investigate the impact of the current strategy fot the elimination of leprosy on its incidence and to assess the consequences of failure to sustain this strategy. Methods: Scenarios for assessing the impact of the elimination strategy were implemented in a coputer simulation program. The scenarios reflected the assumptions made regarding contagiousness, transmission and bacille Calmet-Guerin (BCG) vaccination. The trend in case detection rate for the main countries in which leprosy was endemic during 1985-98 was fitted, and incidence up to 2020 was projected. Findings: Owing to the gradual shortening of delays in detection up to 1998, and because of the low relapse rate that occurs with multidrug treatment MDT, incidence is predicted to decrease beyond 2000 in all scenarios. The annual decline was a few per cent higher when favourable assumptions were made about protection and coverage of BCG vaccination. Overall, the predicted annual decline in incidences ranged from 2% to 12%. Conclusions: The elimination strategy reduces transmission, but the decline amy be slow. Relaxation of control after 2005 is unjustified given the uncertainty about the rate of decline and the adverse effects of longer delays in detection. A long-term strategy for leprosy control should be adopted

Disappearance of leprosy from Norway: an exploration of critical factors using an epidemiological modelling approach.

BACKGROUND: By the middle of the 19th century, leprosy was a serious public health problem in Norway. By 1920, new cases only rarely occurred. This study aims to explain the disappearance of leprosy from Norway. METHODS: Data from the National Leprosy Registry of Norway and population censuses were used. The patient data include year of birth, onset of disease, registration, hospital admission, death, and emigration. The Norwegian data were analysed using epidemiological models of disease transmission and control. RESULTS: The time trend in leprosy new case detection in Norway can be reproduced adequately. The shift in new case detection towards older ages which occurred over time is accounted for by assuming that infected individuals may have a very long incubation period. The decline cannot be explained fully by the Norwegian policy of isolation of patients: an autonomous decrease in transmission, reflecting improvements in for instance living conditions, must also be assumed. The estimated contribution of the isolation policy to the decline in new case detection very much depends on assumptions made on build-up of contagiousness during the incubation period and waning of transmission opportunities due to rapid transmission to close contacts. CONCLUSION: The impact of isolation on interruption of transmission remains uncertain. This uncertainty also applies to contemporary leprosy control that mainly relies on chemotherapy treatment. Further research is needed to establish the impact of leprosy interventions on transmission.

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.