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Impressum

Parasite acquisition & Immunosuppression

Children at the Mein Creek, Liberia
Children at the Mein Creek, Liberia
(Photo: D. W. Büttner)
With processes commonly used to modify the shape of age-dependent parasite distributions, the patterns found in the nodulectomy data for onchocerciasis, can only be explained if unrealistic patterns in age-dependent exposure and heterogeneity in the host population are implemented. On the other hand, there exists a variety of experimental investigations which have suggested parasite-induced immunosuppression to be relevant not only for onchocerciasis, but also for lymphatic filariasis (see literature, below). Parasite-induced immunosuppression could be a phenomenon commonly observable among most of the nematodes.

We assume that immunosuppression induced by the parasite not only affects the parasites which already have infected the host, but moreover promotes the infection with further infectious larvae (L3). Parasite acquisition occurs then density-dependently, i.e. the number of parasites succesfully establishing in a human host per time increases with the parasite burden in the host. It may sound implausible that such a process positively influences the prospects of control success, but the following logic holds:

Control decreases the parasite burden reduces the influence of immunosuppression improves the immunological competence of hosts decreases the infection rate parasite burden decreases accellerated.

Hence, this process does not only promote the parasite's efforts to invade the host population, but also our efforts, to get rid of the parasite. This is a general property of facilitation processes, to whom immunosuppression belongs. Whether or not this process sufficiently increases the prospects of the eradicability of onchocerciasis, depends on the influence of co-existing limitation processes which decrease the prospects of intervention success.
Figure
Density-dependent acquisition of female O. volvulus (left) and corresponding age-intensity profile (right) in the West African savannah village of Kourougbele (Burkina Faso). Blue triangles: boys/men, red circles: girls/women. Bold line: median of the age-specific parasite distributions, thin lines: quantiles 25%, 75% und 97.5% (the 2.5% quantil is very close to the abscissa). Source: Duerr HP et al., 2003b.
Methods: Since the process of density-dependent parasite acquisition is not explicitely solvable, the age-related parasite distributions have been generated by stochastic simulations and implemented into an estimation procedure. This so-called simulation-based maximum-likelihood estimation ("pseudo-likelihood") has so far not routinely been used and needs advanced conseration. The simulation furthermore allowed to consider specific properties of the process of data collection such that a "custom-made" estimation environment for the data could be achieved.

Related pages: Infection with filariae, Age-intensity profiles, Infection rate.

Further reading:
  • Duerr, H. P., Dietz, K., Eichner, M., 2003a. On the interpretation of age-intensity profiles and dispersion patterns in parasitological surveys. Parasitology 126, 87-101. Abstract at PubMed
  • Duerr, H. P., Dietz, K., Schulz-Key, H., Büttner, D. W., Eichner, M., 2003b. Density-dependent parasite establishment suggests infection-associated immunosuppression as an important mechanism for parasite density regulation in onchocerciasis. Trans. R. Soc. Trop. Med. Hyg. 97, 242-250. Abstract at PubMed
Literature:
  • Allen, J. E., MacDonald, A. S., 1998. Profound suppression of cellular proliferation mediated by the secretions of nematodes. Parasite. Immunol. 20, 241-247.
  • Cooper, P. J., Mancero, T., Espinel, M., Sandoval, C., Lovato, R., Guderian, R. H., Nutman, T. B., 2001. Early human infection with Onchocerca volvulus is associated with an enhanced parasite-specific cellular immune response. J. Infect. Dis. 183, 1662-1668.
  • Elkhalifa, M. Y., Ghalib, H. W., Dafa'Alla, T., Williams, J. F., 1991. Suppression of human lymphocyte responses to specific and non-specific stimuli in human onchocerciasis. Clin. Exp. Immunol. 86, 433-439.
  • Hoffmann, W. H., Pfaff, A. W., Schulz-Key, H., Soboslay, P. T., 2001. Determinants for resistance and susceptibility to microfilaraemia in Litomosoides sigmodontis filariasis. Parasitology 122, 641-649.
  • King, C. L., Nutman, T. B., 1991. Regulation of the immune response in lymphatic filariasis and onchocerciasis. Immunol. Today 12, A54-A58.
  • Maizels, R. M., Bundy, D. A., Selkirk, M. E., Smith, D. F., Anderson, R. M., 1993. Immunological modulation and evasion by helminth parasites in human populations. Nature 365, 797-805.
  • Maizels, R. M., Lawrence, R. A., 1991. Immunological tolerance: the key feature in human filariasis? Parasitol. Today 7, 271-276.
  • Piessens, W. F., Ratiwayanto, S., Tuti, S., Palmieri, J. H., Piessens, P. W., Koiman, I., Dennis, D. T., 1980. Antigen-specific suppressor cells and suppressor factors in human filariasis with Brugia malayi. N. Engl. J. Med. 302, 833-837.
  • Schulz-Key, H., Soboslay, P. T., Hoffmann, W. H., 1992. Ivermectin-facilitated immunity. Parasitol. Today 8, 152-153.
  • Soboslay, P. T., Lüder, C. G., Hoffmann, W. H., Michaelis, I., Helling, G., Heuschkel, C., Dreweck, C. M., Blanke, C. H., Pritze, S., Banla, M., Schulz-Key, H., 1994. Ivermectin-facilitated immunity in onchocerciasis; activation of parasite-specific Th1-type responses with subclinical Onchocerca volvulus infection. Clin. Exp. Immunol. 96, 238-244.
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Responsible for this page: Dr. H.-P. Duerr
Webmaster: Prof. Dr. M. Eichner (last change of this page on 13 July 2009)
Cooperation with: Prof. K. Dietz, Institut für Medizinische Biometrie (IMB), Tübingen
Dr. M. Eichner
Further project partners: Prof. H. Schulz-Key, Institute for Tropical Medicine, University of Tübingen, Germany
Prof. D. W. Büttner, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany
Financial support by: Deutsche Forschungsgemeinschaft (DFG, DI 308/12-1)
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