A modelling analysis of a new multi-stage pathway for classifying achievement of public health milestones for leprosy.

Several countries have come close to eliminating leprosy, but leprosy cases continue to be detected at low levels. Due to the long, highly variable delay from infection to detection, the relationship between observed cases and transmission is uncertain. The World Health Organization's new technical guidance provides a path for countries to reach elimination. We use a simple probabilistic model to simulate the stochastic dynamics of detected cases as transmission declines, and evaluate progress through the new public health milestones. In simulations where transmission is halted, 5 years of zero incidence in autochthonous children, combined with 3 years of zero incidence in all ages is a flawed indicator that transmission has halted (54% correctly classified). A further 10 years of only occasional sporadic cases is associated with a high probability of having interrupted transmission (99%). If, however, transmission continues at extremely low levels, it is possible that cases could be misidentified as historic cases from the tail of the incubation period distribution, although misleadingly achieving all three milestones is unlikely (less than 1% probability across a 15-year period of ongoing low-level transmission). These results demonstrate the feasibility and challenges of a phased progression of milestones towards interruption of transmission, allowing assessment of programme status. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Policy Lessons From Quantitative Modeling of Leprosy.

Recent mathematical and statistical modeling of leprosy incidence data provides estimates of the current undiagnosed population and projections of diagnosed cases, as well as ongoing transmission. Furthermore, modeling studies have been used to evaluate the effectiveness of proposed intervention strategies, such as postleprosy exposure prophylaxis and novel diagnostics, relative to current approaches. Such modeling studies have revealed both a slow decline of new cases and a substantial pool of undiagnosed infections. These findings highlight the need for active case detection, particularly targeting leprosy foci, as well as for continued research into innovative accurate, rapid, and cost-effective diagnostics. As leprosy incidence continues to decline, targeted active case detection primarily in foci and connected areas will likely become increasingly important.

Innovative tools and approaches to end the transmission of Mycobacterium leprae.

Leprosy control has seen little innovation and only limited progress in the past decade. However, research on the disease has increased and important innovations are underway. Here, we comment on efforts to develop tools and approaches to detect leprosy and to stop the transmission of Mycobacterium leprae, the causative bacillus of the disease. The tracing and screening of contacts of known patients with leprosy promises to strengthen early diagnosis, while preventive chemotherapy will reduce the risk of contacts developing the disease by 50-60% within 2 years of administration. Until now, diagnosis has been mainly based on the presence of signs and symptoms, but efforts are underway to develop inexpensive, reliable, point-of-care tests to diagnose infection. Development of a leprosy-specific vaccine that boosts long-lasting T-cell responses is also a research objective. As for launching a programme to interrupt transmission, two interlinked tools-epidemiological modelling and the concept of an investment case-are being developed to explore the feasibility and costs of such a programme and its overall effect on individuals and society. We believe that sustained innovation is needed and that only a combination of tools and approaches holds promise to end M leprae transmission.

Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases.

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination 'as a public health problem' when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models' predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020.