Disease Transmission Models for Public Health Decision Making: Toward an Approach for Designing Intervention Strategies for Schistosomiasis Japonica. (Articles)

Spear, Robert C., Hubbard, Alan, Liang, Song, Seto, Edmund, Environmental Health Perspectives

Mathematical models of disease transmission processes can serve as platforms for integration of diverse data, including site-specific information, for the purpose of designing strategies for minimizing transmission. A model describing the transmission of schistosomiasis is adapted to incorporate field data typically developed in disease control efforts in the mountainous regions of Sichuan Province in China, with the object of exploring the feasibility of model-based control strategies. The model is studied using computer simulation methods. Mechanistically based models of this sort typically have a large number of parameters that pose challenges in reducing parametric uncertainty to levels that will produce predictions sufficiently precise to discriminate among competing control options. We describe here an approach to parameter estimation that uses a recently developed statistical procedure called Bayesian melding to sequentially reduce parametric uncertainty as field data are accumulated over several seasons. Preliminary results of applying the approach to a historical data set in southwestern Sichuan are promising. Moreover, technologic advances using the global positioning system, remote sensing, and geographic information systems promise cost-effective improvements in the nature and quality of field data. This, in turn, suggests that the utility of the modeling approach will increase over time. Key words: disease transmission, mathematical models, parameter estimation, schistosomiasis. Environ Health Perspect 110:907-915 (2002). [Online 12 August 2002] http://ehpnet1.niehs.nih.gov/docs/2002/110p907-915spear/abstract.html

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In a companion article, Eisenberg et al. (2002) present an approach to the analysis of infectious disease transmission for waterborne pathogens using dynamic models studied via computer simulation techniques. Here we present an application of this approach to designing local control strategies for the parasitic disease schistosomiasis. The schistosomiasis transmission cycle involves mammals and freshwater snail species linked through contact with different forms of the parasite in surface waters. Our work focuses on agricultural villages in the southwestern part of Sichuan Province in China, where schistosomiasis is endemic. The challenge is to determine whether a dynamic modeling approach can be a useful tool in specifying effective intervention strategies. We propose to use the model to integrate general knowledge of the factors controlling transmission of the disease, quantitative data specific to the transmission of schistosomiasis in China, and site-specific data of the sort typically available in these settings.

This report is of work in progress in that our activities to date have been concerned with model formulation and its parameterization, particularly in light of the kind of field data commonly generated in rural China. We have not yet designed and implemented an intervention program. However, much of our work has been devoted to analysis of data from a study that culminated in a successful intervention program carried out by our colleagues at the Sichuan Institute of Parasitic Disease over 1987-1995. Regrettably, that intervention was not sustainable because of recurrent annual costs of drug treatment. This underscores that the search is for an intervention strategy that is not only effective but also sustainable in a local context.

It is important to point out at the outset that we are not designing intervention trials in a traditional epidemiologic context. Our objective is not to determine whether a particular intervention is effective when all other factors are controlled. For schistosomiasis, there is a considerable body of knowledge about the array of methods of controlling transmission that have been employed in different settings. The task is to determine which blend of the subset of feasible interventions should be used in a particular setting and to predict its probable effectiveness in diminishing disease transmission. To accomplish this task, we require a well-informed computer model of schistosomiasis transmission that can be calibrated to local conditions. Eventually, we hope to use the model as a tool for routinely designing the management strategies for the many sites where the disease is endemic.

The Disease

Schistosomiasis is a waterborne parasitic disease that affects 200 million people and poses a threat to 600 million in more than 76 countries (WHO 1993). The disease is caused by infection by parasitic worms of the genus Schistosoma. These parasites are transmitted via contact with contaminated water. The life cycle of the schistosome begins with the sexual pairing of adult worms in the blood vessels of the host and the production of copious numbers of eggs, a fraction of which are excreted in feces (or urine in the case of S. haematobium). The eggs hatch in water and release a free-swimming miracidium, whose objective in life is to find and penetrate an appropriate snail in which to develop. After a period of asexual reproduction, tailed, free-swimming larvae called cercaria leave the snail and are transported in water, where they actively seek an appropriate vertebrate host. Cercaria penetrate the intact skin of the host, thus infecting it. The parasites subsequently mature into adult worms in the host, where they mate to complete the cycle.

Four to six weeks after schistosome penetration and once worms have migrated to and settled in the mesenteric veins of the vertebrate host, mated adult worms begin to produce eggs. On rare occasions, infected people will experience a severe condition at this time, called Katayama fever, in the Asian form of the disease. The worms themselves cause little or no damage to the body. They are generally undetected by the body's immune system because of the ability of the worm's tegument to attach host proteins to itself as a kind of camouflage. In the long term, it is the eggs that are the real culprits of clinical disease. Eggs are carried off in circulation and are sieved by small blood vessels, especially in the liver and spleen, where the body's immune system attacks them and covers them with fibrotic tissues that accumulate into granulomas.

Long-term infections can lead to development of severe lesions that block blood flow. The resulting increase in blood pressure can in turn direct eggs out of the abdominal area into other parts of the body, including the lungs and brain. The tissue damage and lesion development caused in these areas can be fatal in severe cases. Symptoms of chronic infection may include general malaise; abdominal pain; headache; enlargement of the liver, spleen, and lymph nodes; and presence of blood, pus, and mucus in the stool. Cirrhosis may develop as lesions accumulate in the liver.

In the continuing absence of a vaccine for schistosomiasis, it is necessary to rely on various environmental and behavioral interventions to diminish risk of infection. Virtually all have been tried in one setting or another. Because water contact is the route of exposure of the vertebrate host, it is possible to identify particularly hazardous aquatic environments and attempt to control access to them by both humans and animals. Alternatively, one may either protect the snails from infection by humans and animals or destroy the snails or their habitat. In China, an ancient and pervasive practice involves mixing human excrement, termed nightsoil, with that of animals, which is then used for crop fertilization. Where animal involvement is marginal, this practice is central to maintaining the infection in the snail population. Hence, the strategy of enhancing sanitation facilities and conditions employed in other regions of the world to date has not been a viable strategy in China. More commonly, the large-scale use of chemotherapy for humans and animals has been used and has the beneficial effect of controlling morbidity while interrupting the egg burden shed into the environment. Although various combinations of these control strategies have been used quite successfully to reduce the incidence of disease in China, as recently as 1995 approximately 865,000 people and 100,000 water buffalo were infected (Chen 1999). The endemic areas in 2000 are shown in Figure 1. Control has been particularly difficult in certain regions, including the mountainous areas of Sichuan, where our work has been focused.

[FIGURE 1 OMITTED]

Schistosomiasis is a disease whose distribution is particularly sensitive to environmental change, most clearly environmental change of human origin. Two events loom that promise major environmental changes: the completion of the Three Gorges Dam on the Yangtze River in China and the increasing probability of global warming. The changes that will be caused by these events promise to have a substantial impact on the distribution and extent of S. japonicum in China. Hotez et al. (1997) have written on the impact of the dam, speculating that the effect will generally be to increase both Oncomelania snail habitat and human disease transmission. More recently, …

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Publication information: Article title: Disease Transmission Models for Public Health Decision Making: Toward an Approach for Designing Intervention Strategies for Schistosomiasis Japonica. (Articles). Contributors: Spear, Robert C. - Author, Hubbard, Alan - Author, Liang, Song - Author, Seto, Edmund - Author. Journal title: Environmental Health Perspectives. Volume: 110. Issue: 9 Publication date: September 2002. Page number: 907+. © 2006 National Institute of Environmental Health Sciences. COPYRIGHT 2002 Gale Group.

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