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parasitic infections and inflammatory diseases: the web of immune responses, host genetics and environmental exposure

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Funding (Project expired 2011)
This research project is mainly being funded by the Royal Netherlands Academy of Arts and Sciences (for more information see the brochure "Scientific Programma Indonesia Netherlands - A shared passion for research")
additional financial contribution is obtained from:
- EU funded project COINFECT
- EU funded project TRANCHI
- WOTRO project “Maturation of immune responses in children born to helminth infected mothers: impact on early childhood



About the project (in English) (in Bahasa)
The human immune system is continuously exposed to infectious micro organisms and noxious as well as innocuous substances in the environment. Depending on the genetic makeup, the innate and adaptive immune responses develop and determine the frequency and the course of infectious diseases. It is becoming increasingly clear that certain pathogens causing chronic infections, such as parasitic helminths, have strong immunomodulatory activities affecting responses to co-infections. In many parts of the developing world, malarial and helminth infections are co-endemic and many children are infected by both parasites. We intend to investigate the immunological associations between helminth infections and malarial parasites in coendemic areas of Indonesia to answer the question whether helminths by increasing suppressory immune responses increase susceptibility to malarial parasites on the one hand but protect from cerebral malaria on the other. This central question cannot be addressed in isolation. The immune response is affected by environmental exposure to pollutants and to endotoxin, which are inflammatory triggers. The rural Indonesian household is highly dependent on biomass fuels and associated with relatively poor hygiene; these translate into high exposure to pollutants and endotoxin. It is important to measure how these environments affect the immune system and its interaction with infectious microbes; an area that has not been addressed in developing countries before. Finally, the genetic makeup of an individual plays a key role in how immune responses develop.

We will address the question of how the household environment and host genetics shape the course of helminth/malaria co-infections. We will build into the program a secondary question of how the genetic makeup, environmental exposure and parasitic infections affect inflammatory disorders such as allergic diseases. It is important to realise that Indonesia is a country in transition from one with high burden of infection and traditional lifestyle to one where infectious diseases will be controlled and modern lifestyle will take over bringing along an increase in inflammatory diseases such as allergies and autoimmune diseases. We are therefore keen to build a network program that addresses specific questions on infectious diseases of importance now and inflammatory diseases that are expected to become important in the future, with the view to finding intervention strategies.

flores island Flores Island flores island people

A Collaborative network of 3 Universities in the Netherlands and 2 Universities in Indonesia will bring together experts who will set up multidisciplinary field studies in Flores Island, where semi urban village Nangapanda and rural area of Anaranda will form the bases for epidemiological surveys. These areas are endemic for malarial parasites and helminth infections and provide the unique opportunity of studying the interaction between these infections within distinct environmental contexts in terms of a rural to urban gradient. The Geographical Positioning and Information System (GPS/GIS) will form an integral part of the data collection allowing entry of spatial, demographic, environmental and clinical data. This will allow the generation of maps as part of the multivariate analysis of data to reveal trends, dependencies and inter relationships that otherwise remain hidden in tabular data. The epidemiological surveys will be linked to basic studies in immunology, biochemistry and genetics to understand the molecular mechanisms behind interactions found at the epidemiological level. To this end, immunological micro assays that have been developed for population studies will be applied to gain insight into the innate and adaptive immune system while detailed genomic/proteomic studies of T cell subsets and antigen presenting cells will be performed in subsets of the study population. Indoor environmental samples collected from representative houses will be assessed for their content of carbon pollutants and microbial products using (bio)chemical assays. In vitro models will be set up to verify the specific interactions between immune cells and the environmental factors and to understand the mechanisms downstream of these interactions. For genetic studies, samples will be collected and polymorphisms analysed in family based studies as well as case control designs. Candidate genes involved in control of infections, allergies, pro and anti inflammatory immune responses will be targeted.

The data generated will be analysed within the following conceptual framework to determine multiple relationships among several related and unrelated variables:

Developing countries need to incorporate science, technology and innovation into their economy. It is the mandate of SPIN program to facilitate this process and the current proposal has been developed as a result of equal partnership between Indonesian and Dutch scientists who propose to carry out joint projects of highest scientific quality in the area of health. By generating a pool of young scientists with complementary skills that follow 9 PhD tracks, the program will build capacity for the future.