Voordouw, Maarten

2021, Bregnard, Cindy, Voordouw, Maarten

Les tiques et les maladies transmises par les tiques représentent un problème de santé important pour l'homme et ses animaux de compagnie. Les agents pathogènes transmis par les tiques provoquent une morbidité et une mortalité chez leurs hôtes vertébrés (y compris les humains). L'incidence de la borréliose de Lyme et d'autres maladies transmises par les tiques est en augmentation en Europe et en Amérique du Nord. Afin de prédire le risque de maladies transmises par les tiques, il est essentiel de comprendre les facteurs écologiques qui déterminent l'abondance des tiques ainsi que la densité des tiques infectées, car cette variable détermine le risque de borréliose de Lyme pour les hôtes vertébrés, y compris les humains. En Europe, la tique du mouton (Ixodes ricinus) transmet un certain nombre de maladies importantes, dont la borréliose de Lyme, causée par la bactérie Borrelia burgdorferi sensu lato (sl). En Europe continentale, le stade nymphal de l’espèce de tiques I. ricinus a souvent une phénologie bimodale avec un pic printanier important et un pic automnal plus petit. Il existe un consensus sur l'origine du pic nymphal printanier, mais l'origine du pic nymphal d'automne reste incertaine. Deux hypothèses alternatives prédisent des décalages temporels différents (0 an versus 1 an) entre le pic automnal des tiques nymphales et le repas sanguin du stade précédent (tique larvaire). Le succès d'alimentation des larves de tiques dépend de la densité de leurs hôtes de petits mammifères, qui à son tour dépend de la production de graines (masting) par les arbres à feuilles caduques. Cette thèse de doctorat visait à déterminer les facteurs abiotiques et biotiques qui influencent la variation saisonnière et interannuelle du DON et du DIN dans un endroit en Suisse où la borréliose de Lyme est endémique.
Sur une période de 15 ans (2004 à 2018), nous avons suivi l'abondance mensuelle de l’espèce de tiques I. ricinus (nymphes et adultes) et leur statut infectieux de B. burgdorferi sl à quatre altitudes différentes sur la montagne de Chaumont à Neuchâtel en Suisse romande. Nous avons collecté des variables climatiques sur le terrain et à partir de stations météorologiques à proximité. Nous avons obtenu des données sur la production de graines de hêtres dans la littérature, car l'abondance des nymphes du genre Ixodes peut augmenter considérablement deux ans après un événement de masting. Nous avons utilisé des modèles linéaires généralisés et une sélection de modèles basée sur l'AIC pour identifier les facteurs écologiques qui influencent la variation interannuelle de la densité des nymphes (DON), la densité des nymphes infectées (DIN) et la prévalence de l'infection nymphale (NIP). Nous avons utilisé des modèles additifs généralisés et une sélection de modèles basée sur l'AIC pour modéliser la phénologie saisonnière bimodale complexe des nymphes de l’espèce de tiques I. ricinus et investigué si cette approche fournit des informations supplémentaires sur les facteurs qui expliquent la variation saisonnière de l'abondance des tiques.
Dans le chapitre 1, nous avons constaté que l'altitude, l'année, les événements de masting deux ans auparavant et l'humidité relative expliquaient ensemble 73,2 % de la variation de nos estimations annuelles du DON. Selon les estimations des paramètres de nos modèles, (i) la densité annuelle de nymphes a presque doublé au cours de la période d'étude de 15 ans, (ii) le changement de l'indice de production de graines de hêtre de 1 à 5 a augmenté l'abondance des nymphes de 86,2% deux années plus tard, et (iii) l'augmentation de l'humidité relative recueillie sur le terrain de 50,0% à 75,0% a diminué l'abondance des nymphes de 46,4% au cours de la même année.
Dans le chapitre 2, nous avons constaté que la variation interannuelle du NIP a diminué de 78% au cours de la période d'étude et ceci s’explique par la moyenne des précipitations de l'année en cours, et la durée pendant laquelle l'extraction d'ADN a été stockée dans le congélateur avant la détection de l'agent pathogène. Le DIN a diminué au cours de la période d'étude aux quatre sites d’altitude différente, mais la diminution n'était significative qu'au site d’altitude supérieure. La variation interannuelle du DIN s'expliquait le mieux par le site d'altitude, l'année, les événements de masting deux ans auparavant et l'humidité relative moyenne de l'année en cours.
Dans le chapitre 3, nous avons constaté que les nymphes de l’espèce de tiques I. ricinus avaient une phénologie bimodale aux trois sites d'altitude inférieure, mais une phénologie unimodale au site d'altitude supérieure. Nous avons également constaté que la variation interannuelle des densités de nymphes de l’espèce de tiques I. ricinus à l'automne et au printemps s'expliquait le mieux par un décalage d'un an par rapport à un décalage de 2 ans avec l'indice de masting des hêtres. L'hypothèse du direct development est la meilleure explication du pic automnal des nymphes de l’espèce de tiques I. ricinus sur notre site d'étude. Notre étude fournit un nouvel aperçu de la phénologie bimodale complexe de cet important vecteur de maladie.
Cette thèse de doctorat a démontré que la production de graines par les arbres à feuilles caduques est un facteur critique de l'abondance saisonnière et interannuelle de l’espèce de tiques I. ricinus, et donc du risque de maladie transmise par les tiques. Ce travail fournit de nouvelles informations sur la phénologie bimodale de l’espèce de tiques I. ricinus, en particulier que l'hypothèse du direct development est la meilleure explication des pics printaniers et automnales des nymphes de I. ricinus.

Abstract
Ticks and tick-borne diseases represent a significant health problem for humans and their companion animals. Tick-borne pathogens cause morbidity and mortality in their vertebrate hosts (including humans). The incidence of Lyme borreliosis and other tick-borne diseases is increasing in Europe and North America. To predict the risk of tick-borne disease, it is critical to understand the ecological factors that determine the abundance of ticks and the density of infected ticks as this variable determines the risk of Lyme borreliosis to vertebrate hosts including humans. In Europe, the sheep tick (Ixodes ricinus) transmits a number of important diseases including Lyme borreliosis, which is caused by the bacterium Borrelia burgdorferi sensu lato (sl). In continental Europe, the nymphal stage of I. ricinus often has a bimodal phenology with a large spring peak and a smaller fall peak. There is consensus about the origin of the spring nymphal peak, but the origin of the fall nymphal peak remains unclear. Two alternative hypotheses predict different time lags (0 year versus 1 year) between the fall peak of the nymphal ticks and the blood meal of the previous stage (larval tick). The feeding success of the larval ticks depends on the density of their small mammal hosts, which in turn, depends on the seed production (masting) by deciduous trees. This PhD thesis aimed to determine the abiotic and biotic factors that influence the seasonal and inter-annual variation in the density of nymphs (DON) and density of infected nymphs (DIN) at a location in Switzerland where Lyme borreliosis is endemic.
Over a 15-year period (2004 to 2018), we monitored the monthly abundance of I. ricinus ticks (nymphs and adults) and their B. burgdorferi sl infection status at four different elevations on Chaumont Mountain in Neuchâtel, western Switzerland. We collected climate variables in the field and from nearby weather stations. We obtained data on beech tree seed production (masting) from the literature, as the abundance of Ixodes nymphs can increase dramatically two years after a masting event. We used generalized linear models and AIC-based model selection to identify the ecological factors that influence inter-annual variation in the DON, DIN and, the nymphal infection prevalence (NIP). We used generalized additive models and AIC-based model selection to model the complex bimodal seasonal phenology of I. ricinus nymphs and whether this approach yields additional insights into the factors that explain seasonal variation in tick abundance.
In chapter 1, we found that elevation, year, masting events two years prior, and relative humidity together explained 73.2% of the variation in our annual estimates of the DON. According to the parameter estimates of our models, (i) the annual density of nymphs almost doubled over the 15-year study period, (ii) changing the beech tree seed production index from 1 to 5 increased the abundance of nymphs by 86.2% two years later, and (iii) increasing the field-collected relative humidity from 50.0% to 75.0% decreased the abundance of nymphs by 46.4% in the same year.
In chapter 2, we found that the inter-annual variation in the NIP decreased by 78% over the study period and was explained by the mean precipitation in the present year, and the duration that the DNA extraction was stored in the freezer prior to pathogen detection. The DIN decreased over the study period at all four elevation sites, but the decrease was only significant at the top elevation. Inter-annual variation in the DIN was best explained by elevation site, year, masting events two years prior, and the mean relative humidity in the present year.
In chapter 3, we found that the I. ricinus nymphs had a bimodal phenology at the three lower elevation sites, but a unimodal phenology at the top elevation site. We also found that the inter-annual variation in the densities of I. ricinus nymphs in the fall and spring were best explained by a 1-year versus a 2-year time lag with the beech tree masting index. The direct development hypothesis is the best explanation for the fall peak of I. ricinus nymphs at our study site. Our study provides new insight into the complex bimodal phenology of this important disease vector.
This PhD thesis demonstrated that masting events by deciduous trees is a critical driver of the seasonal and inter-annual abundance of I. ricinus ticks, and hence the risk of tick-borne disease. This work provides new information on the bimodal phenology of I. ricinus ticks, particularly that the direct development hypothesis is the best explanation for the spring and fall peaks of I. ricinus nymphs.

2017, Heylen, D., Sprong, H., Krawczyk, A., Van Houtte, N., Genne, D., Gomez-Chamorro, A., van Oers, K., Voordouw, Maarten

2015-12, Sapsford, Sarah J., Voordouw, Maarten, Alford, Ross A., Schwarzkopf, Lin

Pathogens can drive host population dynamics. Chytridiomycosis is a fungal disease of amphibians that is caused by the fungus Batrachochytrium dendrobatidis (Bd). This pathogen has caused declines and extinctions in some host species whereas other host species coexist with Bd without suffering declines. In the early 1990s, Bd extirpated populations of the endangered common mistfrog, Litoria rheocola, at high-elevation sites, while populations of the species persisted at low-elevation sites. Today, populations have reappeared at many high-elevation sites where they presently co-exist with the fungus. We conducted a capture-mark-recapture (CMR) study of six populations of L. rheocola over 1 year, at high and low elevations. We used multistate CMR models to determine which factors (Bd infection status, site type, and season) influenced rates of frog survival, recapture, infection, and recovery from infection. We observed Bd-induced mortality of individual frogs, but did not find any significant effect of Bd infection on the survival rate of L. rheocola at the population level. Survival and recapture rates depended on site type and season. Infection rate was highest in winter when temperatures were favourable for pathogen growth, and differed among site types. The recovery rate was high (75.7-85.8 %) across seasons, and did not differ among site types. The coexistence of L. rheocola with Bd suggests that (1) frog populations are becoming resistant to the fungus, (2) Bd may have evolved lower virulence, or (3) current environmental conditions may be inhibiting outbreaks of the fatal disease.

2015, Tonetti, Nicolas, Voordouw, Maarten, Durand, Jonas, Monnier, Séverine, Gern, Lise

The vector-to-host and host-to-vector transmission steps are the two critical events that define the life cycle of any vector-borne pathogen. We expect negative genetic correlations between these two transmission phenotypes, if parasite genotypes specialized at invading the vector are less effective at infecting the vertebrate host and vice versa. We used the tick-borne bacterium Borrelia afzelii, a causative agent of Lyme borreliosis in Europe, to test whether genetic trade-offs exist between tick-to-host, systemic (host-to-tick), and a third mode of co-feeding (tick-to-tick) transmission. We worked with six strains of B. afzelii that were differentiated according to their ospC gene. We compared the three components of transmission among the B. afzelii strains using laboratory rodents as the vertebrate host and a laboratory colony of Ixodes ricinus as the tick vector. We used next generation matrix models to combine these transmission components into a single estimate of the reproductive number (R0) for each B. afzelii strain. We also tested whether these strain-specific estimates of R0 were correlated with the strain-specific frequencies in the field. We found significant genetic variation in the three transmission components among the B. afzelii strains. This is the first study to document genetic variation in co-feeding transmission for any tick-borne pathogen. We found no evidence of trade-offs as the three pairwise correlations of the transmission rates were all positive. The R0 values from our laboratory study explained 45% of the variation in the frequencies of the B. afzelii ospC strains in the field. Our study suggests that laboratory estimates of pathogen fitness can predict the distribution of pathogen strains in nature.

2017, Durand, Jonas, Herrmann, C., Genné, D., Sarr, Anouk, Gern, Lise, Voordouw, Maarten

2016-3, Jacquet, Maxime, Durand, Jonas, Rais, Olivier, Voordouw, Maarten

Vector-borne pathogens use a diversity of strategies to evade the vertebrate immune system. Co-feeding transmission is a potential immune evasion strategy because the vector-borne pathogen minimizes the time spent in the vertebrate host. We tested whether the Lyme disease pathogen, Borrelia afzelii, can use co-feeding transmission to escape the acquired immune response in the vertebrate host. We induced a strain-specific, protective antibody response by immunizing mice with one of two variants of OspC (A3 and A10), the highly variable outer surface protein C of Borrelia pathogens. Immunized mice were challenged via tick bite with B.afzelii strains A3 or A10 and infested with larval ticks at days 2 and 34 post-infection to measure co-feeding and systemic transmission respectively. Antibodies against a particular OspC variant significantly reduced co-feeding transmission of the targeted (homologous) strain but not the non-targeted (heterologous) strain. Cross-immunity between OspC antigens had no effect in co-feeding ticks but reduced the spirochaete load twofold in ticks infected via systemic transmission. In summary, OspC-specific antibodies reduced co-feeding transmission of a homologous but not a heterologous strain of B.afzelii. Co-feeding transmission allowed B.afzelii to evade the negative consequences of cross-immunity on the tick spirochaete load.

2015-2-17, Voordouw, Maarten, Lachish, Shelly, Dolan, Marc C.

Zoonotic pathogens that cause devastating morbidity and mortality in humans may be relatively harmless in their natural reservoir hosts. The tick-borne bacterium Borrelia burgdorferi causes Lyme disease in humans but few studies have investigated whether this pathogen reduces the fitness of its reservoir hosts under natural conditions. We analyzed four years of capture-mark-recapture (CMR) data on a population of white-footed mice, Peromyscus leucopus, to test whether B. burgdorferi and its tick vector affect the survival of this important reservoir host. We used a multi-state CMR approach to model mouse survival and mouse infection rates as a function of a variety of ecologically relevant explanatory factors. We found no effect of B. burgdorferi infection or tick burden on the survival of P. leucopus. Our estimates of the probability of infection varied by an order of magnitude (0.051 to 0.535) and were consistent with our understanding of Lyme disease in the Northeastern United States. B. burgdorferi establishes a chronic avirulent infection in their rodent reservoir hosts because this pathogen depends on rodent mobility to achieve transmission to its sedentary tick vector. The estimates of B. burgdorferi infection risk will facilitate future theoretical studies on the epidemiology of Lyme disease.

2017, Jacquet, Maxime, Margos, G., Fingerle, V., Voordouw, Maarten

2015-12, Jacquet, Maxime, Durand, Jonas, Rais, Olivier, Voordouw, Maarten

Cross-reactive acquired immunity in the vertebrate host induces indirect competition between strains of a given pathogen species and is critical for understanding the ecology of mixed infections. In vector-borne diseases, cross-reactive antibodies can reduce pathogen transmission at the vector-to-host and the host-to-vector lifecycle transition. The highly polymorphic, immunodominant, outer surface protein C (OspC) of the tick-borne spirochete bacterium Borrelia afzelii induces a strong antibody response in the vertebrate host. To test how cross-immunity in the vertebrate host influences tick-to-host and host-to-tick transmission, mice were immunized with one of two strain-specific recombinant OspC proteins (A3, A10), challenged via tick bite with one of the two B. afzelii ospC strains (A3, A10), and infested with xenodiagnostic ticks. Immunization with a given rOspC antigen protected mice against homologous strains carrying the same major ospC group allele but provided little or no cross-protection against heterologous strains carrying a different major ospC group allele. There were cross-immunity effects on the tick spirochete load but not on the probability of host-to-tick transmission. The spirochete load in ticks that had fed on mice with cross-immune experience was reduced by a factor of two compared to ticks that had fed on naive control mice. In addition, strain-specific differences in mouse spirochete load, host-to-tick transmission, tick spirochete load, and the OspC-specific IgG response revealed the mechanisms that determine variation in transmission success between strains of B. afzelii. This study shows that cross-immunity in infected vertebrate hosts can reduce pathogen load in the arthropod vector with potential consequences for vector-to-host pathogen transmission. (C) 2015 Elsevier B.V. All rights reserved.

2015-2, Voordouw, Maarten

This review examines the phenomenon of co-feeding transmission in tick-borne pathogens. This mode of transmission is critical for the epidemiology of several tick-borne viruses but its importance for Borrelia burgdorferi sensu lato, the causative agents of Lyme borreliosis, is still controversial. The molecular mechanisms and ecological factors that facilitate co-feeding transmission are therefore examined with particular emphasis on Borrelia pathogens. Comparison of climate, tick ecology and experimental infection work suggests that co-feeding transmission is more important in European than North American systems of Lyme borreliosis, which potentially explains why this topic has gained more traction in the former continent than the latter. While new theory shows that co-feeding transmission makes a modest contribution to Borrelia fitness, recent experimental work has revealed new ecological contexts where natural selection might favour co-feeding transmission. In particular, co-feeding transmission might confer a fitness advantage in the Darwinian competition among strains in mixed infections. Future studies should investigate the ecological conditions that favour the evolution of this fascinating mode of transmission in tick-borne pathogens.