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Tuesday 6 Sept 2022

Tuesday 06 Sep

07:30

Venue open

Pathogenesis

Chair: Linden Hu (USA)

08:50

Short introduction chair

Linden Hu (USA)

09:00

Understanding mechanism underlying acute Lyme disease and chronic symptoms

Klemen Strle (USA)

ABSTRACT

Background: Patients with Lyme borreliosis may present with a range of clinical manifestations which vary in severity and duration, including complications which persist after antibiotic therapy for the infection. The reasons for this heterogeneity are not well understood, but host immune responses are thought to play an important role. Herein we focus on our recent longitudinal study of immune responses in patients with Lyme neuroborreliosis (LNB), approximately 20% of whom may experience symptoms that persist despite appropriate antibiotic therapy, including pain, fatigue, and neurocognitive deficits.

Methods: Seventy nine patients with LNB, 28 with persistent symptoms and 51 without, were followed systematically from the initial visit prior to antibiotic therapy for 1 year thereafter to evaluate their clinical course and outcome. Patients with lingering symptoms and those without were evaluated by clinical, laboratory, and demographic characteristics. In addition, the levels of 20 inflammatory mediators associated with innate and adaptive immune responses were determined in matched serum and cerebrospinal fluid (CSF) to test the possibility that lingering symptoms after LNB are due to maladaptive immune responses triggered during the infection.

Results: At study entry, most inflammatory mediators were highly concentrated in CSF, the site of the disease. These responses resolved with antibiotic therapy, and the associations between CSF cytokines and signs and symptoms of LNB were no longer observed. In contrast, symptoms that persisted after antibiotics were associated with elevated IFNα levels in serum, which were already observed at study entry (median=18 vs 2 pg/ml, p=.01) and remained elevated at each subsequent timepoint. When stratified by severity, patients with the most severe post-Lyme symptoms which required regular use of analgesics had the highest levels of IFNα, whereas those whose symptoms resolved had the lowest IFNα levels (p=0.006). Finally, post-treatment symptoms occurred more frequently in women, and in those with a highly symptomatic preceding infection (odds ratio=4.8), but were not associated with borrelia culture positivity or with other clinical, laboratory, or immunologic abnormalities in CSF. These findings imply that although the infection serves as the initial trigger, post-LNB complications likely result from sustained maladaptive immune responses in blood.

Conclusion: Debilitating sequelae after LNB are associated with unremitting systemic levels of IFNα, consistent with the pathogenic role of this cytokine in Type1 interferonopathies in other infectious and autoimmune conditions. The emergence of data supporting the role of immune response in post-Lyme sequelae may provide new considerations for treatment approaches which prioritize targeting the immune response after appropriate antibiotic regimens, a treatment algorithm currently used effectively in treatment of post-antibiotic Lyme arthritis.

09:30

Selected abstracts

09:50

Selected abstracts

10:10

Selected abstracts

10:20

Break

Ecology

Chair: Jean Tsao (USA)

10:50

Short introduction chair

Jean Tsao (USA)

11:00

Transmission dynamics of B. burgdorferi s.s.

Maarten Voordouw (Canada)

Borrelia burgdorferi sensu lato is a complex of tick-borne spirochetes that include the causative agents of Lyme borreliosis. B. burgdorferi is maintained in nature by enzootic cycles that include hard ticks in the genus Ixodes and vertebrate reservoir hosts. The life cycle of B. burgdorferi includes two critical steps: (1) transmission from an infected host to naïve larvae and (2) transmission from an infected nymph to a naïve host. Host-to-tick transmission (HTT) can be measured by infesting infected hosts with larval ticks and determining the percentage of ticks that acquire the infection. Tick-to-host transmission (THT) is inherently more difficult to quantify. B. burgdorferi has a high reproduction number (R0) compared to other tick-borne pathogens because it establishes a chronic infection in the reservoir host with high HTT.

In endemic areas, B. burgdorferi populations often consist of a dozen antigenically distinct strains that circulate in the same vertebrate host and tick populations. Comparative studies with multiple strains allow us to better understand how natural selection shapes the life history traits of B. burgdorferi. Our studies have found that strains that establish higher abundance in the tissues of the vertebrate reservoir host have higher transmission to feeding ticks. Similarly, strains that establish a higher abundance in the nymphs have a higher probability of being transmitted to naïve reservoir hosts.

In nature, co-infections with multiple strains of the same B. burgorferi species are common in both tick vectors and vertebrate reservoir hosts. Co-infection results in competitive interactions where the presence of one strain reduces the fitness of the other strain and vice versa. Co-infections in the vertebrate host reduce the abundance of strains in the host tissues, which in turn reduces the strain-specific probability of HTT. The strain that wins the competition for transmission to ticks is the one that establishes the higher abundance in the tissues of the co-infected rodent host, but whether this result is general remains unknown. In summary, the ability to maintain high abundance in the host tissues and the nymphal tick is critical for strains to have high transmission success in both steps of the tick-borne life cycle.

11:30

Selected abstract

11:50

Selected abstract

Poster Pitches

12:20

t.b.c.

12:22

t.b.c.

12:24

t.b.c.

12:26

t.b.c.

12:28

t.b.c.

12:30

t.b.c.

12:30

Lunch & Posters

Tick biology

Chair: Olaf Kahl (Germany)

14:30

Short introduction chair

Olaf Kahl (Germany)

14:40

Intricate tick-host-pathogen interactions in LD

Utpal Pal (USA)

15:10

Selected abstract

15:30

Selected abstract

15:40

Selected abstract

16:00

Break

Lyme in the Lymelight

Hein Sprong & Joppe Hovius (Netherlands)

16:30

Short introduction chairs

Hein Sprong & Joppe Hovius (Netherlands)

16:40

Selected abstract

17:00

Selected abstract

17:20

Chronic B. burgdorferi sl infection, lessons from animal models?

Monica Embers (USA)

17:40

Closing