The L1 larval stage of Trichinella spiralis induces modification in a portion of striated skeletal muscle cell resulting in the formation of the nurse cell. This specialized host cell is completely encased in a capsule composed mainly of collagen type IV and type VI, which, in turn, is surrounded by a unique rete of vessels whose formation begins on around day 12 after intracellular infection. We investigated the possibility that vascular endothelial growth factor (VEGF) may be up-regulated during nurse cell formation by employing immunohistochemistry and in situ hybridization on synchronously infected mouse muscle tissue. Both VEGF mRNA and VEGF peptide were detected in the developing nurse cell cytoplasm from day 7 up to 16 mo after infection. In addition, VEGF was also detected in cells in the area immediately surrounding the nurse cell on days 15 and 17. On the basis of these results, we propose that hypoxia is induced by T. spiralis within the developing nurse cell some time prior to the up-regulation of VEGF, perhaps as early as day 7. We further propose, on the basis of the continued presence of VEGF in nurse cell cytoplasm, that a constant state of hypoxia cell is maintained.
Isolated cases and outbreaks of infection with Trichinella spp. occur frequently throughout the world, sometimes resulting in fatalities. The clinical presentations of signs and symptoms are remarkably constant for most of the species of Trichinella, but in infections with Trichinella nativa and Trichinella britovi, classical symptoms of trichinellosis may be absent. It is important to be able to correlate the clinical presentation of trichinellosis with the life cycle of these helminths in order to make an accurate diagnosis. Knowledge of the epidemiology of the disease enables the physician to identify other potential cases, since most epidemics can be traced back to a common source of raw or undercooked meat. A comprehensive summary relating the most important clinical variables is presented graphically for easy reference to the text. Symptoms and signs are considered in relation to severity of infection. Laboratory findings and diagnostic techniques, including new modalities (e.g., DNA and antigen detection), are discussed. A discussion of treatment and preventive measures concludes our review.
Invasion of vertebrate muscle cells by larvae of Trichinella spiralis is accompanied by redifferentiation of the host myofiber into a novel structure called the nurse cell. The nurse cell protects and nurtures the enclosed parasite during its long stay in host muscle. It is anatomically independent of the surrounding uninfected muscle cells and can be isolated from host tissue by mechanical or enzymatic means. Current methods employed for this purpose have yielded only small numbers of nurse cells. An apparatus designed to isolate large numbers of nurse cells and a method for removal of all free larvae and most host muscle debris is described. Homogenization and trypsin digestion of muscle tissue was followed by passage of muscle/parasite suspensions maintained at 37 C through a jacketed glass column fitted with a 40-mesh stainless steel screen at the top and a Nitex screen with 150-microns-diameter pores at the bottom. Nurse cells were retained by the Nitex screen. Density gradient centrifugation using Percoll removed all free larvae and most contaminating muscle debris from nurse cell suspensions. The large quantities of nurse cells made available by this method will allow evaluation of the molecular biology, nutrition, biochemistry, and metabolism of the enclosed parasite and of the Trichinella-modified host muscle cell.
Trichinella spiralis is an intracellular parasite as both a larva and an adult. The first-stage larva lives in a modified portion of a skeletal muscle cell, the nurse cell, and can reside there for the life span of the host. Adult worms occupy a nonmembrane-bound portion of columnar epithelium, living there as intramulticellular parasites. The newborn larva is the only nonintracellular stage, living free in the circulation. Trichinella spiralis induces modifications in each of its intracellular niches. Parasite signals secreted into the milieu of the developing nurse cell results in the reprogramming of host genomic expression, reflected in loss of muscle-specific proteins, over-expression of collagen, and the development of a circulatory rete. Formation of the nurse cell is complex, presumably involving many steps; yet there is not a large series of related intermediate forms in nature. Trichinella pseudospiralis induces an incomplete nurse cell. Adult parasites cause the death of the infected epithelium. The precise nature of most of the signals from parasite to host and from host to parasite has not been determined. As a direct consequence of exposure to some of them, the host develops long-lasting immunity to reinfection. This may confer advantages both for the parasite, as well as the host, because strong immune responses should reduce intraspecific competition.
The Society has recently established a permanent Education Committee to respond to the growing need for dissemination of information regarding tropical and travel medicine. At the ASTMH Retreat several Educational Committee members of the Council—Michele Barry, Jay Keystone, Peter Weller, MacWilson Warren, and Dickson Despommier—set about the task of identifying groups in need of our educational efforts defining educational objectives and translating these into achievable goals and outlining various approaches for the delivery of education programs. The first effort was to identify consumer groups to which educational efforts might be directed, namely graduate students, research scientists, residents, house staff, and practicing physicians, especially those interested in tropical medicine. Several potential vehicles for such an effort were identified, including pre- and post-meeting workshops, plenary sessions as well as symposia on specific educationally relevant topics at the annual meeting and the Journal.
A diagnosis of neurocysticercosis, commonly caused by the larva of the pork tapeworm, Taenia solium, is rare enough to qualify for presentation at grand rounds in most medical centers throughout the United States. However, in Latin America and South Africa,1 it is a frequent cause of clinical manifestations arising from lesions in the central nervous system. Two reports in this issue of the Journal focus attention on the facts that this condition remains a major health threat throughout Mexico2 and that one need not live there to be at risk of this serious, occasionally life-threatening disease.3 In the United . . .
Trichinella spiralis is one of the world's largest intracellular parasites. Unlike most such organisms, it does not kill the host cell, but induces modifications in cell structure that enhance its own survival. In this article, Dickson Despommier describes the ways in which the parasite uses the cell for its own benefit, and discusses the extent to which this behaviour has contributed to the parasite's success.
KATZ, MICHAEL MD; DESPOMMIER, DICKSON D. PHD; DECKELBAUM, RICHARD J. MD Author Information
Highly effective recombinant vaccines have been developed against the helminth parasites Taenia ovis, Taenia saginata and Echinococcus granulosus. These vaccines indicate that it is possible to achieve a reliable, high level of protection against a complex metazoan parasite using defined recombinant antigens. However, the effectiveness of the vaccines against the taeniid cestodes stands in contrast to the more limited successes which characterise attempts to develop vaccines against other platyhelminth or nematode parasites. This review examines the features of the host–parasite relationships among the taeniid cestodes which have formed the basis for vaccine development. Particular consideration is given to the methodologies that have been used in making the cestode vaccines that might be of interest to researchers working on vaccination against other helminths. In developing the cestode vaccines, antigens from the parasites’ infective larval stage contained within the egg (oncosphere) were identified as having the potential to induce high levels of protection in vaccinated hosts. A series of vaccination trials with antigen fractions, and associated immunological analyses, identified individual protective antigens or fractions. These were cloned from cDNA and the recombinant proteins expressed in Escherichia coli. This strategy was independently successful in developing vaccines against T. ovis and E. granulosus. Identification of protective antigens for these species enabled rapid identification, cloning and expression of their homologues in related species and thereby the development of effective vaccines against T. saginata, E. multilocularis and, more recently, T. solium. The T. saginata vaccine provides an excellent example of the use of two antigen components, each of which were not protective when used individually, but when combined they induce a reliable, high level of protection. One important contributing factor to the success of vaccine development for the taeniid cestodes was the concentration on studies seeking to identify native host-protective antigens, before the adoption of recombinant methodologies. The cestode vaccines are being developed towards practical (commercial) application. The high level of efficacy of the vaccines against T. solium cysticercosis and hydatid disease suggests that they would be effective also if used directly in humans.