The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and sub-tropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tubingen to develop a new test method to detect malaria parasites in blood. The idea of the research project, NanoFRET, is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Fluorescent nanoparticles, excited by UV light. (Credit: K. Dobberke for Fraunhofer ISC)

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases. An early diagnosis is vital for the timely and right kind of therapy. There are five different types of parasites at the origin of the disease. Plasmodium falciparum is causing malaria tropica, and it is particularly harmful for infants and pregnant women in the African sub-Saharan region.

To diagnose malaria with conventional diagnostic tools and to identify the parasite causing the infection takes experienced and well-trained personnel and a well-equipped laboratory. Both are scarce in Africa or even anywhere else outside specialized health-care centers.

That is the reason why the NanoFRET project partners come together to develop the whole blood rapid diagnostic test to detect just this special type of parasite. In the body, infectious germs produce large amounts of specific proteins that accumulate in the blood. These proteins will be detected by a new tool developed by the project consortium led by the project coordinator Dr. Rolf Fendel from the University of Tubingen. At Fraunhofer IME, the team around Dr. Torsten Klockenbring sets out to develop antibodies able to identify proteins from the malaria parasite. These antibodies are coupled to novel fluorescent nanoparticles, which Dr. Sofia Dembski and her Theranostik team — part of the Translational Center Regenerative Therapies — developed at the Fraunhofer ISC.

The detection of the pathogen in a blood sample will be based on a special technique (time-resolved fluorescence resonance energy transfer (TR-FRET) in combination with the antibodies and the nanoparticles. However, there is one challenge to overcome: The fluorescent properties of the nanoparticles have to be adapted so that the autofluorescence of blood cannot affect the result.

The spectrometer shows the dye’s fluorescent signal in the excited state. (Credit: Fraunhofer ISC)

Testing will take place with samples from malaria patients and a noninfected control group. Samples will be gathered, characterized and used to define the test parameters. The study will be performed by Dr. Andrea Kreidenweiss from the Institute of Tropical Medicine (University of Tübingen) at the Centre de Recherches Médicales de Lambaréné (CERMEL) located in Gabon, a collaboration partner of long standing.

Upon establishing a reliable method, the next step for the researchers will to test the method in a diagnostic study at the CERMEL. The evaluation will consider sensitivity, specificity, and practicability under real conditions.

If the test proves to be suitable, the project partners will design a prototype kit. They say the test kit must be producible at a low cost and should enable an early diagnosis with malaria tropica.

The project is planned to be completed by late 2019. If successful, the project partners will adapt the test method to other infectious diseases and then find industry partners to develop the next generation of rapid diagnostic tools. Funding is granted by the German Federal Ministry of Education and Research (BMBF) within the framework of the VIP+ program (“Validation of the innovation potential of scientific research”).

Project partners include Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany; Institute of Tropical Medicine at the University of Tübingen, Germany; and Fraunhofer Institute for Silicate Research ISC, Wurzburg, Germany.

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