The LYMFASIM Simulation Program for Modeling Lymphatic Filariasis and its Control

Abstract:

The LYMFASIM modeling framework for the transmission and control of the tropical parasitic disease lymphatic filariasis is described and its use in the context of an endemic community in north-eastern Brazil is illustrated. Lymphatic filariasis is a disease with a complex natural history with many unknowns. This complicates decision making with respect to control strategies. With LYMFASIM, a variety of hypotheses can be tested about the life history of the parasite Wuchereria bancrofti, its transmission from man to man through mosquitoes, the role of the immune system in regulating parasite numbers, the development of disease symptoms, and the effects of control measures (drug treatment or mosquito control). The implications of alternative assumptions and uncertainty about the quantification of parameters for the effectiveness of control strategies can be investigated. Thanks to the use of stochastic microsimulation, LYMFASIM is highly flexible and can be adapted and extended as new knowledge emerges.

Keywords

Lymphatic Filariasis - Tropical Disease - Simulation - Modeling - Decision Making

• REFERENCES

• 1 WHO. Lymphatic Filariasis: The disease and its control. Geneva: World Health Organization; 1992
• 2 Hairston NG, Jachowski LA. Analysis of the Wuchereria bancrofti population in the people of American Samoa. Bull Wld Hlth Org 1968; 38: 29-59.
• 3 Cao W, Van der Ploeg CPB, Plaisier AP, Van der Sluijs US, Habbema JDF. Ivermectin for the chemotherapy of bancroftian filariasis: a meta-analysis of the effect of single treatment. Trop Med Int Hlth 1997; 2: 393-403.
• 4 Day KP. The endemic normal in lymphatic filariasis: a static concept. Parasitol Today 1991; 7: 341-3.
• 5 Grenfell BT, Michael E, Denham DA. A model for the dynamics of human lymphatic filariasis. Parasitol Today 1991; 7: 318-23.
• 6 Ottesen EA. The Wellcome Trust Lecture. Infection and disease in lymphatic filariasis: an immunological perspective. Parasitology 1992; 104: S71-9.
• 7 Maizels RM, Lawrence RA. Immunological tolerance: the key feature in human filariasis?. Parasitol Today 1991; 7: 271-6.
• 8 Day KP, Grenfell B, Spark R, Kazura JW, Alpers MP. Age specific patterns of change in the dynamics of Wuchereria bancrofti infection in Papua New Guinea. Am J Trop Med Hyg 1991; 44: 518-27.
• 9 Bundy DAP, Grenfell BT, Rajagopalan PK. Immuno-epidemiology of lymphatic filariasis: the relationship between infection and disease. In: Ash C, Gallagher RB. eds. Immunoparasitology Today. Cambridge: Elsevier Trends Journals; 1991: A71-A75.
• 10 Srividya A, Pani SP, Rajagopalan PK, Bundy DAP, Grenfell BT. The dynamics of infection and disease in Bancroftian filariasis. Trans Roy Soc Trop Med Hyg 1991; 85: 255-9.
• 11 Habbema JDF, De Vlas SJ, Plaisier AP, Van Oortmarssen GJ. The microsimulation approach to epidemiological modelling of helminthic infections, with special reference to schistosomiasis. Am J Trop Med Hyg 1996; 55: 165-9.
• 12 Plaisier AP, Van Oortmarssen GJ, Habbema JDF, Remme J, Alley ES. ONCHOSIM: a model and computer simulation program for the transmission and control of onchocerciasis. Comp Meth Prog Biomed 1990; 31: 43-56.
• 13 Remme JHF, Alley ES, Plaisier AP. Estimation and prediction in tropical disease control: the example of onchocerciasis. In: Mollison D. ed. Epidemic Models – their Structure and Relation to Data. Cambridge: Cambridge University Press; 1995: 372-93.
• 14 Southgate BA, Bryan JH. Factors affecting transmission of Wuchereria bancrofti by anopheline mosquitoes. 4. Facilitation, limitation, proportionality and their epidemiological significance. Trans Roy Soc Trop Med Hyg 1992; 86: 523-30.
• 15 Subramanian S, Manoharan A, Ramaiah KD, Das PK. Rates of acquisition and loss of Wuchereria bancrofti infection in Culex quinquefasciatus. Am J Trop Med Hyg 1994; 51: 244-9.
• 16 Woolhouse MEJ. A theoretical framework for the immuno-epidemiology of helminth infection. Parasite Immunol 1992; 14: 563-78.
• 17 Haarbrink M, Terhell AJ, Abadi K, Van Beers S, Asri M, Yazdanbaksh M. IgG4 antibody assay in the detection of filariasis. Lancet 1995; 346: 853-4.
• 18 Ottesen EA, Ramachandran CP. Lymphatic filariasis infection and disease: control strategies. Parasitol Today 1995; 11: 129-31.
• 19 Subramanian S, Krishnamoorthy K, Ramaiah KD, Habbema JDF, Das PK, Plaisier AP. The relationship between microfilaria load in the human host and uptake and development of Wuchereria bancrofti microfilariae by Culex quinquefasciatus. A study under natural conditions. Parasitology (in press).
• 20 Plaisier AP, Alley ES, Boatin BA. et al. Irreversible effects of Ivermectin on adult parasites in onchocerciasis patients in the Onchocerciasis Control Programme in West Africa. J Inf Dis 1995; 172: 204-10.
• 21 Law AM, Kelton WD. Simulation Modelling and Analysis. New York: McGraw Hill; 1982
• 22 Kleijnen JPC. Experimental design for sensitivity analysis, optimization, and validation of simulation models. In: Banks J. ed. Handbook of Simulation. New York: Wiley; 1997
• 23 Barton RR, Ivey JS. Nelder-Mead simplex modifications for simulation optimization. Management Sci 1996; 42: 954-73.
• 24 Plaisier AP, van Oortmarssen GJ, Remme J, Alley ES, Habbema JDF. The risk and dynamics of onchocerciasis recrudescence after cessation of vector control. Bull Wld Hlth Org 1991; 69: 169-78.
• 25 Plaisier AP, Alley ES, van Oortmarssen GJ, Boatin BA, Habbema JDF. Required duration of combined annual ivermectin treatment and vector control in the Onchocerciasis Control Programme in West Africa. Bull Wld Hlth Org 1997; 75: 237-45.
• 26 Albuquerque MFM, Marzochi MC, Sabroza PC, et al. Bancroftian filariasis in two urban areas of Recife, Northeastern Brazil: precontrol observations on infection and disease. Trans Roy Soc Trop Med Hyg 1995; 89: 373-7.
• 27 Plaisier AP, van Oortmarssen GJ, Remme J, Habbema JDF. The reproductive lifespan of Onchocerca volvulus in West African savanna. Acta Trop 1991; 48: 271-84.
• 28 Grenfell BT, Michael E. Infection and disease in lymphatic filariasis: an epidemiological approach. Parasitology 1992; 104: S81-S90.
• 29 Muench H. Catalytic Models in Epidemiology. Cambridge Mas: Harvard University Press; 1959
• 30 Vanamail P, Subramanian S, Das PK, et al. Estimation of age-specific rates of acquisition and loss of Wuchereria bancrofti infection. Trans Roy Soc Trop Med Hyg 1989; 83: 689-93.
• 31 Subramanian S, Pani SP, Das PK, Rajagopalan PK. Bancroftian filariasis in Pondicherry, South India: 2. Epidemiological evaluation of the effect of vector control. Epidem Inf 1989; 103: 693-702.
• 32 Pani SP, Yuvaraj J, Vanamail P, et al. Episodic adenolymphangitis and lymphoedema in patients with bancroftian filariasis. Trans Roy Soc Trop Med Hyg 1995; 89: 72-4.
• 33 Hightower AW, Lammie PJ, Eberhard ML. Maternal filarial infection – a persistent risk factor for microfilaraemia in off spring?. Parasitol Today 1993; 9: 418-21.