If the host population is taken to be a dynamic variable (rather than constant, as conventionally assumed), a wider understanding of the population biology of infectious diseases emerges. In this first part of a two-part article, mathematical models are developed, shown to fit data from laboratory experiments, and used to explore the evolutionary relations among transmission parameters. In the second part of the article, to be published in next week's issue, the models are extended to include indirectly transmitted infections, and the general implications for infectious diseases are considered.

Population biology of infectious diseases: Part II

It has been argued that females should be able to choose parasite-resistant mates on the basis of the quality of male secondary sexual characters and that such signals must be costly handicaps in order to evolve. To a large extent, handicap hypotheses have relied on energetic explanations for these costs. Here, we have presented a phenomenological model, operating on an intraspecific level, which views the cost of secondary sexual development from an endocrinological perspective. The primary androgenic hormone, testosterone, has a dualistic effect; it stimulates development of characteristics used in sexual selection while reducing immu- nocompetence. This "double-edged sword" creates a physiological trade-off that influences and is influenced by parasite burden. We propose a negative-feedback loop between signal intensity and parasite burden by suggesting that testosterone-dependent signal intensity is a plastic re- sponse. This response is modified in accordance with the competing demands of the potential costs of parasite infection versus that of increased reproductive success afforded by exaggerated signals. We clarify how this trade-off is intimately involved in the evolution of secondary sexual characteristics and how it may explain some of the equivocal empirical results that have surfaced in attempts to quantify parasite's effect on sexual selection.

Parasites, bright males, and the immunocompetence handicap

In the face of continuous threats from parasites, hosts have evolved an elaborate series of preventative and controlling measures - the immune system - in order to reduce the fitness costs of parasitism. However, these measures do have associated costs. Viewing an individual's immune response to parasites as being subject to optimization in the face of other demands offers potential insights into mechanisms of life history trade-offs, sexual selection, parasite-mediated selection and population dynamics. We discuss some recent results that have been obtained by practitioners of this approach in natural and semi-natural populations, and suggest some ways in which this field may progress in the near future.

Ecological immunology: costly parasite defences and trade-offs in evolutionary ecology

http://www.bio.umass.edu/micro/klingbeil/590s/Reading/Bethony2006.pdf

Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm

[Crohn's disease].

Infestation of the gastrointestinal tract by parasitic nematodes is invariably associated with mucosal mastocytosis1,2, which is a thymus-dependent phenomenon in parasitized rats3, and is adoptively transferable with a T cell-enriched population of thoracic duct lymphocytes4. When derived by in vitro culture, mucosal mast cells (MMC) arise from a bone marrow precursor after stimulation by T cell-derived factors5. In rats infected with the nematode Trichinella spiralis, mucosal mastocytosis is temporally associated with the immune expulsion of the adult worms6 whereas in the case of Nippostrongylus brasiliensis, mastocytosis is frequently observed to occur after worm expulsion has been completed7–9. Consequently, there has been doubt as to whether MMC are active and serve a functional role in the expulsion of rat intestinal nematodes. MMC contain and secrete a neutral proteinase, rat mast cell protease II (RMCPII)10–13; detection and assay of secreted RMCPII therefore provides a direct measurement of MMC activity. Here we describe the release of this enzyme into the blood of rats infected with N. brasiliensis or T. spiralis. Our results show that the systemic secretion of RMCP II coincides with the immune expulsion of these nematodes, demonstrating clearly for the first time that rat MMC are functionally active during the immune elimination of primary nematode infections.

Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in rat

Trichinella spiralis is a highly successful parasite in that it can establish, develop, and reproduce in a wide range of vertebrate hosts. This low host specificity implies that the organism has the ability to adapt to a variety of environmental conditions and hence is relatively unaffected by many of those aspects of natural immunity that impose a more rigid specificity on other species. However, in common with all metazoan parasites, T. spiralis presents the host with a complex antigenic stimulus and thus evokes a powerful immune response. The complexity of the stimulus arises not only from the diversity of antigens present at any one time, but also from the fact that antigens may show stage specificity, changing qualitatively and quantitatively throughout development, and may be released in different tissues of the body. Many components of the immunological response probably have little or no effect on either host or parasite, though they may prove useful in diagnosis; some are deleterious to the parasite and provide protective resistance against infection, yet others are actually or potentially harmful to the host, either from their involvement in immunopathological reactions or through their modulation of unrelated immune responses. This chapter will concentrate on those responses that confer resistance on the host; immune responses in the contexts of diagnosis and pathology are dealt

The Immune Response

https://nottingham-repository.worktribe.com/preview/1024995/Behnke_et_al_1992._IJP_22_861._Understanding_chronic_infections.pdf

Understanding chronic nematode infections: evolutionary considerations, current hypotheses and the way forward.

Patients with postinfective irritable bowel syndrome and Trichinella spiralis-infected mice share many features including visceral hypersensitivity and disordered motility. We assessed enterochromaffin (EC) numbers and serotonin transporter (SERT) using National Institute of Health (NIH) female mice studied for up to 56 days post-T. spiralis infection. The effects of steroid treatment and the T-cell dependence of the observed responses were assessed by infection of hydrocortisone-treated or T-cell receptor knock out [TCR (betaxdelta) KO] animals. Enterochromaffin cell density in uninfected animals increased from duodenum 10.0 cells mm-2 (5.9-41.0) to colon 61.8. (46.3-162) cells mm-2 P<0.0001. Infection increased duodenal and jejunal counts which rose to 37.3 (22-57.7) cells mm-2 and 50.6 (7-110.8) cells mm-2, respectively, at day 14. Infection significantly reduced jejunal SERT expression, with luminance values falling from 61.0 (45.1-98.3) to a nadir of 11.6 (0-36.0) units at day 9, P<0.001. Specific deficiencies in all T cells reduced EC hyperplasia and abrogated infection-induced mastocytosis. Thus infection induced inflammation increases EC numbers, as has been reported in PI-IBS, and reduces SERT. This may increase mucosal 5HT availability and contribute to the clinical presentation of PI-IBS.

Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction.

Intestinal parasites are common in man and animals and can cause severe disease. Knowledge of immunity to such infections is limited and comes largely from studies using laboratory host-parasite systems. Understanding how immunity can operate, and why it often does not, is not only of intrinsic interest but necessary for the development of immunological methods of control.

Derek Wakelin

Papers

Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in rat

The Immune Response

Understanding chronic nematode infections: evolutionary considerations, current hypotheses and the way forward.

Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction.

Immunity to intestinal parasites