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Over the last years, research activities in filariosis started to extend beyond the field of onchocerciasis. Therefore, the Institute’s esearch programme II was named "Filariasis Programme". All three sections of the Bernhard Nocht Institute (BNI) are involved in this programme. The many cooperations between the individuals project groups are documented in several publications. Researchers involved in the programme were invited to international meetings as speakers or chairpersons. Two habilitation scholarships, one Heisenberg fellowship and a scholarship within the career development programme infectious diseases (DKFZ/BMBF) were awarded to members of the Filariasis Programme.
A major topic in 1998 was the identification and analysis of functionally relevant and/or immunogenic Onchocerca volvulus proteins, since these molecules could become the basis of a vaccine or a new chemotherapeutic approach. A growth-regulating protein-kinase was cloned; its Caenorrhabditis elegans homologue is known to be involved in transmission of sensory stimuli. An elastase was partially purified which could prove important for the migration of microfilariae through the tissue. Scavenger enzymes of O. volvulus (peroxidoxin, glutathion-S-transferase, superoxide dismutase) were further characterized with regard to localization (immunohistology), biochemical function and/or stress inducibility (promoter analysis). S-adenosylmethionine-decarboxylase was identified as a target for chemotherapeutical intervention; inhibitors of this molecule are being tested in cooperation with a pharmaceutical company. A new approach is being pursued by the identification of O. volvulus genes which are induced following ivermectin therapy.
Although many immune reactions associated with different courses of infection in human onchocerciasis have been well characterized, it is largely unclear which is the relevance of these reactions in an in vivo situation. These questions need an animal model to be resolved. Using a murine model of filariasis (infection with filariae of the species Litomosoides sigmodontis), it could be shown that two cytokines, IL-5 and IFN-g , are essential for the formation of inflammatoiry nodules around adult worms. The structure of these nodules resembles that in onchocerciasis nodules. In addition to inducing migration of eosinophil granulocytes, IL-5 is also essential for the activation of neutrophils, a hitherto unknown function of this cytokine.
Diagnosis of lymphatic filariasis has been facilitated recently by the advent of a quick and easy test kit; however, this kit detects only infections with Wuchereria bancrofti, not with Brugia malayi . With regard to the latter infection, the situation may improve by a sensitive and specific PCR-ELISA test being developed in cooperation with one of the BNI researchers.
Finally, an area which has gained a lot of interest and which may lead to a novel chemotherapeutic approach, is the cooperative analysis (by molecular biology, immunohistology, biological function) of intracellular bacteria. These organisms belonging to the species of Wolbachia and are found in most filarial species. Sequence analyses of 16 S rRNA revealed that these bacteria have apparently been existing as intracellular simbionts within filarial worms since approx. 50 Mio. years and have diverged into different species together with their hosts. Several genes of bacterial origin have been cloned; antibodies against the expressed proteins allowed to localize the bacteria in immunhistology. The close relationship of Wolbachia to Rickettsiae was exploited for experimental chemotherapy using tetracycline antibiotics in an animal model (L . sigmodontis). This therapy led to an elimination of the bacteria and to a major developmental block of the worms, leading to infertility of female worms. A clinical trial is under way in Ghana to investigate if the elimination of Wolbachia by tetracycline could evolve into a therapeutic approach also in human onchocerciasis.
Achim Hoerauf
| Scientific Staff
Dr. Achim Hoerauf, Medical Microbiology, Coordinator
Visiting Scientist Coralie Martin, Biologie Parasitaire, Protistologie,
Technical Staff
Doctoral / Graduate Students Khaled M. Al-Qaoud, Medical Microbiology
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Immunohistochemical localization
of intracellular bacteria in O. volvulus and L. sigmodontis
filarial nematodes.
(A) Midbody cross-section of an adult
O.
volvulus female, 150x. Bacteria are stained in the lateral and median
hypodermal cords (lhc, mhc), but not in the cuticle (cu), the intestine
(in), the uteri (ut), and the musculature (mu).
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