The QRS response of the electrocardiogram to bleeding has been a source of interest to the physiologist for more than a century. Studies in the dog, cat and chicken have shown a reduction in QRS amplitude in response to bleeding. This effect has been explained by the so-called Brody effect, in which the intraventricular mass of blood acts as a conducting medium, augmenting radial conduction, thus resulting in the subsequent reduction in QRS amplitude in conditions where the intraventricular mass of blood is reduced. The aim of this study was to evaluate whether the Brody effect will be present in the ovine heart and, furthermore, to evaluate if the right and left ventricles will demonstrate the same QRS change if the Brody effect is indeed present. This study clearly demonstrated that the Brody effect is present in the ovine heart. Furthermore, two unique aspects emanating from this study are firstly the fact that this is the first study to show that premature ventricular complexes are able to induce the Brody effect and, secondly that there is a very clear difference in the response of the right and the left ventricles when the Brody effect is induced in the ovine heart.

Although Theiler became internationally known for his pioneering veterinary research a distant century ago, there are probably few veterinary researchers today who have not heard of him. Onderstepoort, the research institute he created, is equally well, if not even better, known. Moreover, the name Onderstepoort is not only associated with his institute but also with the only South African faculty of veterinary science, another Theiler 'baby'. The purpose of this presentation is to determine why this was so, and to what extent the fame was justified. Was it due to the 'Spirit of Onderstepoort' sometimes referred to by Theiler in the early as well as later stages of his career, or was there perhaps more to it, and what was Theiler's share in the development of that spirit, that fame?

Tsetse-fly and the disease it transmits, trypanosomosis, remain an enormous disease challenge in the 37 countries of sub-Saharan Africa where the impact continues to be manifest in disease burden, increased level of poverty and decreased agricultural productivity. The impact also extends over an estimated 10 million km² (a third of the African continent) of land area, a third of which contains some well-watered part of the continent, thus denying humans and livestock of potentially rich arable and pastureland. The disease is a threat to an estimated 50 million people and 48 million cattle with estimated annual losses in cattle production alone of 1-1.2 billion US$. These losses are due to stock mortality and depressed productivity, which may be of meat, milk, reproduction or traction. Beyond its direct effects on humans and livestock is its impact on African agriculture and the livelihood of the rural population in the affected countries: the fly and the disease influence where people decide to live, how they manage their livestock, and the intensity and the mix of crop agriculture. The combined effects result in changes in land use and environment which may, in turn, affect human welfare and increase the vulnerability of agricultural activity. Trypanosomosis is, therefore, both a public health and an agricultural development constraint. The challenges that the elimination or control of tsetse fly and trypanosomosis pose as well as the opportunities to develop appropriate intervention technologies are discussed in this presentation.

The use of new, highly sensitive diagnostic methods has revealed persistent infections to be a common feature of different tick-borne diseases, such as babesiosis, anaplasmosis and heartwater. Antigenic variation can contribute to disease persistence through the continual elaboration of new surface structures, and we know in several instances how this is achieved. Known or suspected mechanisms of persistence in babesial parasites include cytoadhesion and rapid variation of the adhesive ligand in Babesia bovis and genetic diversity in several merozoite stage proteins of different Babesia spp. In Anaplasma, extensive variation in the pfam01617 gene family accompanies cycling of organism levels in chronic infection. One result from the pioneering research at Onderstepoort is the definition of a related polymorphic gene family that is likely involved in immunity against heartwater disease. We are beginning to understand the sizes of the antigenic repertoires and full definition is close, with the possibility of applying simultaneous high-throughput sequencing to the order of 1 000 small genomes. We also, for the first time, can consider modifying these genomes and looking at effects on persistence and virulence. However, important biological questions remain unanswered; for example, why we are seeing a new emerging Anaplasma infection of humans and is infection of endothelial cells by Anaplasma significant to persistence in vivo.

Eighty ixodid tick species, 25 argasid tick species and Nuttalliella namaqua occur in South Africa. Twenty-one of the 80 ixodid species and two of the argasid species occur only in this country, while N. namaqua is present only in South Africa and Namibia. Forty-six of the 80 ixodid species and 16 of the 25 argasid species as well as N. namaqua have been described as new species since 1908. People working in South Africa have written or contributed to the descriptions of 24 of these 63 new species, while foreign researchers have described the remainder. New species indigenous to South Africa are still being discovered, while the names of some species, well known because of their veterinary importance, have been altered.

Sir Arnold Theiler's research in 1908/09 led to the discovery of the first rickettsial pathogen, Anaplasma marginale, and set the stage for his development and implementation of an effective live vaccine based on a less virulent strain, A. marginale ss. centrale. His 1910 report, describing A. marginale, is among the classic monographs in infectious disease research, presenting not only observations in exacting detail but also highlighting the deductive reasoning leading to association of a new pathogen with a specific disease. With a centennial perspective and both conceptual frameworks and molecular tools unimaginable in Theiler's time, the significance of several observations in the original report- cyclic bacteremia, strain superinfection, and taxonomic position-is now clear and highlight the broad applicability of key principles of pathogen biology.

Heartwater is an economically serious tick-borne disease of ruminants caused by the intracellular bacterium Ehrlichia ruminantium. The disease has traditionally been controlled by four different approaches: controlling the tick vector by dipping, establishing endemic stability, performing immunisation by infection and treatment, and preventing the disease by regular administration of prophylactic antibiotics. The first three of these methods are subject to failure for various epidemiological reasons, and serious disease outbreaks can occur. Prophylaxis is effective, but very expensive, and the logistics are daunting when large herds of animals are involved. The development of a safe, cheap and effective vaccine is the only likely way in which heartwater can be economically controlled, and over the past 15 years three new types of experimental vaccine have been developed: inactivated, attenuated, and recombinant vaccines. These new vaccines have shown varying degrees of promise, but none is as yet sufficiently successful to be marketable. We describe the experimental products, and the various technical and biological difficulties which are being encountered, and report on ways in which new technologies are being used to improve vaccine effectiveness.