Advances and challenges in predicting the impact of lymphatic filariasis elimination programmes by mathematical modelling

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, P,O, Box 2040, 3000 CA Rotterdam, The Netherlands.
Filaria Journal 03/2006; 5(1):5. DOI: 10.1186/1475-2883-5-5
Source: PubMed


Mathematical simulation models for transmission and control of lymphatic filariasis are useful tools for studying the prospects of lymphatic filariasis elimination. Two simulation models are currently being used. The first, EPIFIL, is a population-based, deterministic model that simulates average trends in infection intensity over time. The second, LYMFASIM, is an individual-based, stochastic model that simulates acquisition and loss of infection for each individual in the simulated population, taking account of individual characteristics. For settings like Pondicherry (India), where Wuchereria bancrofti infection is transmitted by Culex quinquefasciatus, the models give similar predictions of the coverage and number of treatment rounds required to bring microfilaraemia prevalence below a level of 0.5%. Nevertheless, published estimates of the duration of mass treatment required for elimination differed, due to the use of different indicators for elimination (EPIFIL: microfilaraemia prevalence < 0.5% after the last treatment; LYMFASIM: reduction of microfilaraemia prevalence to zero, within 40 years after the start of mass treatment). The two main challenges for future modelling work are: 1) quantification and validation of the models for other regions, for investigation of elimination prospects in situations with other vector-parasite combinations and endemicity levels than in Pondicherry; 2) application of the models to address a range of programmatic issues related to the monitoring and evaluation of ongoing control programmes. The models' usefulness could be enhanced by several extensions; inclusion of different diagnostic tests and natural history of disease in the models is of particular relevance.

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    • "Poor treatment compliance rates (Ramaiah et al. 2000a, b) and persistence of microfilaremia after 4–5 rounds of mass drug administration (MDA) necessitate rethinking on the adequacy of four to six annual rounds of treatment, which is believed to be sufficient for eliminating LF. Intervention efforts need to be strengthened by prolonging the MDA or supplementing intervention measures (Stolk et al. 2006; Ramaiah et al. 2007), apart from improving compliance to over 80% which is central to move toward elimination of LF (El-Setouhy et al. 2007). Post-MDA-I survey results in one of the endemic islands for DspWB filariasis in the Nancowry group of islands showed microfilaremia prevalence ranging between 3.2% and 23.1% in different villages with a mean parasite intensity of 37.31 (range 1–492)/60 mm 3 among the microfilaremics. "
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    ABSTRACT: The elimination of lymphatic filariasis in the Andaman and Nicobar Islands provides unique opportunities and challenges at the same time. Since these islands are remote, are sparsely populated, and have poor transport networks, mass drug administration programs are likely to be difficult to implement. Diurnally subperiodic Wuchereria bancrofti vectored by Downsiomyia nivea was considered for the scope of vector control options. Considering the bioecology of this mosquito, vector control including personal protection measures may not be feasible. However, since these islands are covered by separate administrative machinery which also plays an important role in regulating the food supply, the use of diethylcarbamazine (DEC)-fortified salt as a tool for the interruption of transmission is appealing. DEC-fortified salt has been successfully pilot tested in India and elsewhere, operationally used by China for eliminating lymphatic filariasis. Administration of DEC-fortified salt though simple, rapid, safe, and cost-effective, challenges are to be tackled for translating this precept into action by evolving operationally feasible strategy. Although the use of DEC-fortified salt is conceptually simple, it requires commitment of all sections of the society, an elaborate distribution mechanism that ensures the use of DEC-fortified salt only in the endemic communities, and a vigorous monitoring mechanism. Here, we examine the inbuilt administrative mechanisms to serve the tribal people, health infrastructure, and public distribution system and discuss the prospects of putting in place an operationally feasible strategy for its elimination.
    Parasitology Research 02/2011; 109(1):1-8. DOI:10.1007/s00436-011-2252-4 · 2.10 Impact Factor
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    • "transmission dynamics (Southgate, 1992 ; Snow and Michael, 2002 ; Snow et al. 2006). To support decision making in the elimination programmes worldwide , we need vector-parasite specific, validated model variants (Dadzie et al. 2004 ; Stolk, de Vlas and Habbema, 2006). "
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    ABSTRACT: LYMFASIM is a simulation model for lymphatic filariasis transmission and control. We quantified its parameters to simulate Wuchereria bancrofti transmission by Anopheles mosquitoes in African villages, using a wide variety of reported data. The developed model captures the general epidemiological patterns, but also the differences between communities. It was calibrated to represent the relationship between mosquito biting rate and the prevalence of microfilariae (mf) in the human population, the age-pattern in mf prevalence, and the relation between mf prevalence and geometric mean mf intensity. Explorative simulations suggest that the impact of mass treatment depends strongly on the mosquito biting rate and on the assumed coverage, compliance and efficacy. Our sensitivity analysis showed that some biological parameters strongly influence the predicted equilibrium pre-treatment mf prevalence (e.g. the lifespan of adult worms and mf). Other parameters primarily affect the post-treatment trends (e.g. severity of density dependence in the mosquito uptake of infection from the human blood, between-person variability in exposure to mosquito bites). The longitudinal data, which are being collected for evaluation of ongoing elimination programmes, can help to further validate the model. The model can help to assess when ongoing elimination activities in African populations can be stopped and to design surveillance schemes. It can be a valuable tool for decision making in the Global Programme to Eliminate Lymphatic Filariasis.
    Parasitology 12/2008; 135(13):1583-98. DOI:10.1017/S0031182008000437 · 2.56 Impact Factor
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    • "Recently Stolk et al[7] compared EPIFIL and LYMFASIM in terms of their structure and parameter quantifications and highlighted deficiencies that impede their wide spread application for decision support. These authors found that, despite differences in model structure and parameterization, both models were able to predict the duration of control required for elimination under assumptions based on current biological understanding. "
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    ABSTRACT: Mathematical models developed for describing the dynamics of transmission, infection, disease and control of lymphatic filariasis (LF) gained momentum following the 1997 World Health Assembly resolution and the launching of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) in 2000. Model applications could provide valuable inputs for making decisions while implementing large scale programmes. However these models need to be evaluated at different epidemiological settings for optimization and fine-tuning with new knowledge and understanding on infection/disease dynamics. EPIFIL and LYMFASIM are the two mathematical simulation models currently available for lymphatic filariasis transmission and control. Both models have been used for prediction and evaluation of control programmes under research settings. Their widespread application in evaluating large-scale elimination programmes warrants validation of assumptions governing the dynamics of infection and disease in different epidemiological settings. Furthermore, the predictive power of the models for decision support can be enhanced by generating knowledge on some important issues that pose challenges and incorporating such knowledge into the models. We highlight factors related to the efficacy of the drugs of choice, their mode of action, and the possibility that drug resistance may develop; the role of vector-parasite combinations; the magnitude of transmission thresholds; host-parasite interactions and their effects on the dynamics of infection and immunity; parasite biology, and progression to LF-associated disease. The two mathematical models developed offer potential decision making tools for transmission and control of LF. In view of the goals of the GPELF, the predictive power of these models needs to be enhanced for their wide-spread application in large scale programmes. Assimilation and translation of new information into the models is a continuous process for which generation of new knowledge on a number of uncertainties is required. Particularly, a better understanding of the role of immune mechanisms in regulating infection and disease, the (direct or immune mediated) mode of action of current drugs, their effect on adult worms, their efficacy after repeated treatment, and the population genetics of drug resistance are important factors that could make the models more robust in their predictions of the impact of programmes to eliminate LF. However, if these models are to be user-friendly in the hands of programme managers (and not remain as research tools), it would be necessary to identify those factors which can be considered as the minimum necessary inputs/outputs in operational settings for easy evaluation and on-site decision making.
    Parasites & Vectors 02/2008; 1(1):2. DOI:10.1186/1756-3305-1-2 · 3.43 Impact Factor
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