Jeremy S. Gray

Lyme borreliosis: Clinical case definitions for diagnosis and management in Europe

Lyme borreliosis, caused by spirochaetes of the Borrelia burgdorferi genospecies complex, is the most commonly reported tick-borne infection in Europe and North America. The non-specific nature of many of its clinical manifestations presents a diagnostic challenge and concise case definitions are essential for its satisfactory management. Lyme borreliosis is very similar in Europe and North America but the greater variety of genospecies in Europe leads to some important differences in clinical presentation. These new case definitions for European Lyme borreliosis emphasise recognition of clinical manifestations supported by relevant laboratory criteria and may be used in a clinical setting and also for epidemiological investigations.

Babesiosis: recent insights into an ancient disease.

Ever since the discovery of parasitic inclusions in erythrocytes of cattle in Romania by Victor Babes at the end of the 19th century, newly recognised babesial pathogens continue to emerge around the world and the substantial public health impact of babesiosis on livestock and man is ongoing. Babesia are transmitted by ixodid ticks and infection of the host causes a host-mediated pathology and erythrocyte lysis, resulting in anemia, hyperbilirubinuria, hemoglobinuria, and possibly organ failure. Recently obtained molecular data, particularly for the 18S rRNA gene, has contributed significantly to a better understanding of the sometimes puzzling phylogenetic situation of the genus Babesia and new information has been added to help determine the taxonomic position of many species. Moreover, it seems that owing to higher medical awareness the number of reported cases in humans is rising steadily. Hitherto unknown zoonotic babesias are now being reported from geographical areas where babesiosis was not known to occur and the growing numbers of immunocompromised individuals suggest that the frequency of cases will continue to rise. This review covers recent insights into human babesiosis with regard to phylogeny, diagnostics and treatment in order to provide new information on well known as well as recently discovered parasites with zoonotic potential.

The ecology of ticks transmitting Lyme borreliosis.

The main vectors of Borrelia burgdorferi sensu lato, the cause of Lyme borreliosis, are ixodid ticks of the Ixodes persulcatus species complex. These ticks, which occur throughout the northern temperate zone, have very similar life cycles and ecological requirements. All are three-host ticks, with the immature stages mainly parasitizing small to medium-sized mammals and birds and the adult females parasitizing large mammals such as deer, cattle, sheep and hares. The host-seeking stages show a distinct seasonality, which is regulated by diapause mechanisms and there appear to be major differences in this respect between the Old World and New World species. Most cases of human borreliosis are transmitted in the summer by the nymphal stages, with the exception of the Eurasian species, I. persulcatus, in which the adult females are mainly responsible. The ticks acquire the spirochaetes from a wide variety of mammals and birds but large mammals do not seem to be infective, so that t icks that feed almost exclusively on large mammals, for example in some agricultural habitats, are rarely infected. The greatest tick infection prevalences occur in deciduous woodland harbouring a diverse mix of host species and the diversity of the different genospecies of B. burgdorferi s.l. is also greatest in such habitats. There is evidence that these genospecies have different host predilections but, apart from the fact that I. persulcatus does not seem to be infected by B. burgdorferi sensu stricto, they do not seem to be adapted to different tick strains or species.

Zoonotic babesiosis: Overview of the disease and novel aspects of pathogen identity

Babesiosis is a zoonosis caused by tick-transmitted intraerythrocytic protozoa of the Phylum Apicomplexa. The disease mostly occurs in the USA, but cases have also been reported in several European countries, in Egypt, India, Japan, Korea, Taiwan, and South Africa. The main pathological event is lysis of erythrocytes resulting in haemolytic anaemia, which in severe cases may lead to organ failure and death, particularly in immunocompromised patients. The 2 groups of parasites involved, Babesia microti-like and Babesia sensu stricto (s.s.) species, differ in their life cycle characteristics and susceptibility to antibabesial drugs. Molecular taxonomy is now making a major contribution to the identification of novel pathogens within both groups. Effective treatment of severe cases was initially hampered by the lack of specific antibabesial drugs for human use, but increased use of supportive measures and of the recently developed antimalarial, atovaquone, particularly in combination with azithromycin, has improved the prospects for management of acute disease especially when caused by Babesia s.s. species. Prevention should be based primarily on increasing the awareness of physicians and the public to the risks, but infection from blood transfusions is particularly difficult to prevent. Expanding deer populations, resulting in wider distribution and greater abundance of ticks, heightened medical awareness, and growing numbers of immunocompromised patients are likely to result in a continuing rise of reported cases.

Risk of infection with Borrelia burgdorferi sensu lato for a host in relation to the duration of nymphal Ixodes ricinus feeding and the method of tick removal.

The objectives of the present study were to investigate the risk of B. burgdorferi s.1. (Bb)-transmission by I. ricinus-nymphs to a host (i) after different periods of feeding, and (ii) with regard to the particular method of tick removal. On each of 72 Mongolian gerbils 3 tick nymphs taken from a highly infected batch were allowed to feed in a small capsule. Feeding ticks were removed 16.7, 28.9, 47.0, and 65.2 hrs post-attachment. In each of these 4 groups 3 sub-groups with 6 gerbils each were deticked by (a) pulling ticks out with forceps without any pretreatment, (b) pulling ticks out after 3 min of intensive squeezing, and (c) applying nail polish to ticks 1.1 hrs before removal. The infection status in each gerbil was subsequently determined by larval xenodiagnosis. All gerbils with ticks removed > or = 47 hrs post-attachment were found to be infected. After 16.7 hrs as well as after 28.9 hrs of tick feeding, approximately 50% of the gerbils had acquired a transmissible infection, thus Bb-transmission to a host may even occur in the early phases of I. ricinus feeding. There is no evidence from this study that the tick removal method used has any significant influence on a hosts Bb-infection risk.

Epidemiology of European Lyme borreliosis.

Lyme borreliosis occurs throughout Europe and is particularly prevalent in the east. In a small proportion of untreated cases serious sequelae may occur, but Lyme borreliosis alone does not cause death. Clinical and serological diagnosis can still be problematic and the various genomospecies may cause different disease manifestations as well as differing immunological responses. However, considerable progress has been made in standardising case definitions and serological testing and interpretation. Few countries have official reporting systems for Lyme borreliosis and most figures on incidence are extrapolated from serodiagnosis data and seroprevalence studies. Geographical variations in incidence seem to correlate with the prevalence of infected ticks, which are mainly associated with varied deciduous forest. The complex ecology of Lyme borreliosis makes it difficult to implement preventive measures, so improving public knowledge of risk factors and methods for personal protection remain the best option at present.

Lyme borreliosis habitat assessment

Tick ecologists throughout Europe provided descriptions of Lyme borreliosis habitats according to a standardised format and data for 105 habitats in 16 countries were received. The data showed that high risk situations, as defined by the presence of large numbers of B. burgdorferi sensu lato-infected nymphal I. ricinus, occur in heterogeneous deciduous woodland, usually with a recreational function and with a diverse fauna, usually including deer. Large numbers of ticks occurred in some other habitats, but infection prevalence was usually low. The situation for adult I. ricinus was similar but less clearly defined. Tick infection rates were found to be lower in western Europe than in the east, and the infection rate in I. persulcatus, the most easterly vector species, was markedly higher than in I. ricinus. In the vast majority of habitats the infection rate in adult I. ricinus was greater than in nymphs. Larvae were rarely found to be infected.

Ecology of Borrelia burgdorferi sensu lato in Europe: transmission dynamics in multi-host systems, influence of molecular processes and effects of climate change.

The analysis of different multi-host systems suggests that even hosts that are not capable of transmitting Borrelia burgdorferi sensu lato (s.l.) to the tick vector, Ixodes ricinus, or that are secondary reservoirs for these agents contribute to the intensity of transmission and to the overall risk of Lyme borreliosis, through the process of vector augmentation and pathogen amplification. On the other hand, above certain threshold densities, or in the presence of competition with primary reservoir hosts or low attachment rate of ticks to reservoir hosts, incompetent or less competent hosts may reduce transmission through dilution. The transmission of B. burgdorferi s.l. is affected by molecular processes at the tick-host interface including mechanisms for the protection of spirochaetes against the hosts immune response. Molecular biology also increasingly provides important identification tools for the study of tick-borne disease agents. Ixodes ricinus and B. burgdorferi s.l. are expanding their geographical range to northern latitudes and to higher altitudes through the effects of climate change on host populations and on tick development, survival and seasonal activity. The integration of quantitative ecology with molecular methodology is central to a better understanding of the factors that determine the main components of Lyme borreliosis eco-epidemiology and should result in more accurate predictions of the effects of climate change on the circulation of pathogens in nature.

Identification of Borrelia burgdorferi sensu lato species in Europe

Characterisation at the species level of 142 Borrelia isolates obtained from ticks, humans and rodents in Western Europe was carried out and their geographical distribution was described. Borrelia garinii was the predominant species representing 44% of the isolates and B. afzelii and B. burgdorferi sensu stricto constituted 27% and 19% of isolates respectively. B. valaisiana, (formerly group VS116) constituted 10.5% of isolates. Some differences in the Borrelia species distribution were observed from one country to another, possibly linked to different sources of samples. In the human samples, which were mostly collected in Austria, B. afzelii was preferentially isolated from skin and B. garinii from CSF. B. afzelii was consistently isolated from rodents captured in Switzerland, but one isolate of B. garinii was obtained from a rodent in Austria. B. garinii was by far the most abundant species isolated from Ixodes ricinus ticks in all studied countries. B. valaisiana was isolated from I. ricinus ticks collected from vegetation and from I. ricinus engorged on birds.

Borrelia burgdorferi sensu lato in Ixodes ricinus ticks and rodents in a recreational park in south-western Ireland

Ixodes ricinus ticks infected with Borrelia burgdorferi sensu lato were numerous on the edges of paths and roads in a recreational park in south-western Ireland. The abundance of ticks at different sites was related to the presence of deer, but a negative relationship was shown between tick abundance and tick infection rates. This is thought to be due to the deposition of large numbers of uninfected ticks by deer, which are apparently not good reservoir hosts of B. burgdorferi s.l. Blood meal analysis only detected deer DNA in uninfected nymphs. Reservoir competent rodents, Apodemus sylvaticus and Clethrionomys glareolus, were abundant at all sites and a high proportion of captured specimens were infested with larval ticks. However, very few rodents were infected with B. burgdorferi s.l. and none of the unfed infected nymphs analysed for the identity of their larval blood meal had fed on rodents. The spirochaetes detected in I. ricinus in the study area may be poorly adapted to rodents or are not transmitted readily because of the absence of nymphal infestation. The majority of spirochaetes in these ticks were apparently acquired from non-rodent hosts, such as birds.