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      Mathematical modelling of lymphatic filariasis elimination programmes in India: required duration of mass drug administration and post-treatment level of infection indicators

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          Abstract

          Background

          India has made great progress towards the elimination of lymphatic filariasis. By 2015, most endemic districts had completed at least five annual rounds of mass drug administration (MDA). The next challenge is to determine when MDA can be stopped. We performed a simulation study with the individual-based model LYMFASIM to help clarify this.

          Methods

          We used a model-variant for Indian settings. We considered different hypotheses on detectability of antigenaemia (Ag) in relation to underlying adult worm burden, choosing the most likely hypothesis by comparing the model predicted association between community-level microfilaraemia (Mf) and antigenaemia (Ag) prevalence levels to observed data (collated from literature). Next, we estimated how long MDA must be continued in order to achieve elimination in different transmission settings and what Mf and Ag prevalence may still remain 1 year after the last required MDA round. The robustness of key-outcomes was assessed in a sensitivity analysis.

          Results

          Our model matched observed data qualitatively well when we assumed an Ag detection rate of 50 % for single worm infections, which increases with the number of adult worms (modelled by relating detection to the presence of female worms). The required duration of annual MDA increased with higher baseline endemicity and lower coverage (varying between 2 and 12 rounds), while the remaining residual infection 1 year after the last required treatment declined with transmission intensity. For low and high transmission settings, the median residual infection levels were 1.0 % and 0.4 % (Mf prevalence in the 5+ population), and 3.5 % and 2.0 % (Ag prevalence in 6–7 year-old children).

          Conclusion

          To achieve elimination in high transmission settings, MDA must be continued longer and infection levels must be reduced to lower levels than in low-endemic communities. Although our simulations were for Indian settings, qualitatively similar patterns are also expected in other areas. This should be taken into account in decision algorithms to define whether MDA can be interrupted. Transmission assessment surveys should ideally be targeted to communities with the highest pre-control transmission levels, to minimize the risk of programme failure.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13071-016-1768-y) contains supplementary material, which is available to authorized users.

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          Most cited references77

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          Strategies and tools for the control/elimination of lymphatic filariasis.

          Lymphatic filariasis infects 120 million people in 73 countries worldwide and continues to be a worsening problem, especially in Africa and the Indian subcontinent. Elephantiasis, lymphoedema, and genital pathology afflict 44 million men, women and children; another 76 million have parasites in their blood and hidden internal damage to their lymphatic and renal systems. In the past, tools and strategies for the control of the condition were inadequate, but over the last 10 years dramatic research advances have led to new understanding about the severity and impact of the disease, new diagnostic and monitoring tools, and, most importantly, new treatment tools and control strategies. The new strategy aims both at transmission control through community-wide (mass) treatment programmes and at disease control through individual patient management. Annual single-dose co-administration of two drugs (ivermectin + diethylcarbamazine (DEC) or albendazole) reduces blood microfilariae by 99% for a full year; even a single dose of one drug (ivermectin or DEC) administered annually can result in 90% reductions; field studies confirm that such reduction of microfilarial loads and prevalence can interrupt transmission. New approaches to disease control, based on preventing bacterial superinfection, can now halt or even reverse the lymphoedema and elephantiasis sequelae of filarial infection. Recognizing these remarkable technical advances, the successes of recent control programmes, and the biological factors favouring elimination of this infection, the Fiftieth World Health Assembly recently called on WHO and its Member States to establish as a priority the global elimination of lymphatic filariasis as a public health problem.
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            The ICT Filariasis Test: A rapid-format antigen test for diagnosis of bancroftian filariasis.

            Antigen testing is now recognized as the method of choice for detection of Wuchereria bancrofti infections. Unlike tests that detect microfilariae, antigen tests can be performed with blood collected during the day or night. However, existing enzyme-linked immunosorbent assay (ELISA) tests for filarial antigenemia are difficult to perform in the field, and this has limited their use in endemic countries. In this article, Gary Weil, Patrick Lammie and Niggi Weiss review their experience with a new rapid-format filarial antigen test. They found that the ICT card test was very easy to perform and that it was comparable with ELISA for the detection of filarial antigen in sera from people with microfilaremia. The introduction now of an antigen test suitable for use in the field is especially timely, in that it may facilitate implementation of new strategies proposed by the World Health Organization for control and elimination of lymphatic filariasis.
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              Mathematical modelling and the control of lymphatic filariasis.

              The current global initiative to eliminate lymphatic filariasis represents one of the largest mass drug administration programmes ever conceived for the control of a parasitic disease. Yet, it is still not known whether the WHO-recommended primary strategy of applying annual single-dose mass chemotherapy with a combination of two drugs for 4-6 years will effectively break parasite transmission from all endemic communities. Here we review recent work on the development and application of a deterministic mathematical model of filariasis transmission, to show how models of parasite transmission will help resolve the key currently debated questions regarding the ultimate effectiveness of the global strategy to control filariasis. These critical questions include the required duration of mass treatment in different endemic areas, the optimal drug coverage required to meet control targets within prescribed timeframes, the impact and importance of adding vector control to mass chemotherapy regimens, and the likelihood of the development of drug resistance by treated worm populations. The results demonstrate the vital role that integrating these models into control programming can have in providing effective decision-support frameworks for undertaking the optimal design and monitoring of regional and global filariasis-control programmes. Operationally, the models show that the effectiveness of the strategy to achieve filariasis control will be determined by successfully addressing two key factors: the need to maintain high community treatment coverages, and the need to include vector control measures especially in areas of high endemicity.
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                Author and article information

                Contributors
                pcsaja@gmail.com
                ssubra@yahoo.com
                s.devlas@erasmusmc.nl
                c.vinubala@gmail.com
                w.stolk@erasmusmc.nl
                Journal
                Parasit Vectors
                Parasit Vectors
                Parasites & Vectors
                BioMed Central (London )
                1756-3305
                13 September 2016
                13 September 2016
                2016
                : 9
                : 1
                : 501
                Affiliations
                [1 ]Vector Control Research Centre (Indian Council of Medical Research), Indira Nagar, Puducherry, 605006 India
                [2 ]Department of Public Health, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
                Article
                1768
                10.1186/s13071-016-1768-y
                5022201
                27624157
                3b4bdc96-2303-43a9-87be-4c724f85d3b8
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 November 2015
                : 22 August 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP1053230, Amendment No. 2 (NTD Modelling Consortium Supplement)
                Award ID: OPP1053230, Amendment No. 2 (NTD Modelling Consortium Supplement)
                Award ID: OPP1053230, Amendment No. 2 (NTD Modelling Consortium Supplement)
                Award ID: OPP1053230, Amendment No. 2 (NTD Modelling Consortium Supplement)
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2016

                Parasitology
                lymphatic filariasis,wuchereria bancrofti,culex quinquefasciatus,india,individual-based model,mass treatment,diethylcarbamazine and albendazole,elimination,prevalence,mda duration,post-mda residual infection

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