Continued Circulation of Tick-Borne Encephalitis Virus Variants and Detection of Novel Transmission Foci, the Netherlands.

Tick-borne encephalitis virus (TBEV) is an emerging pathogen that was first detected in ticks and humans in the Netherlands in 2015 (ticks) and 2016 (humans). To learn more about its distribution and prevalence in the Netherlands, we conducted large-scale surveillance in ticks and rodents during August 2018-September 2020. We tested 320 wild rodents and >46,000 ticks from 48 locations considered to be at high risk for TBEV circulation. We found TBEV RNA in 3 rodents (0.9%) and 7 tick pools (minimum infection rate 0.02%) from 5 geographically distinct foci. Phylogenetic analyses indicated that 3 different variants of the TBEV-Eu subtype circulate in the Netherlands, suggesting multiple independent introductions. Combined with recent human cases outside known TBEV hotspots, our data demonstrate that the distribution of TBEV in the Netherlands is more widespread than previously thought.

Detection of tick-borne encephalitis virus in ear tissue and dried blood spots from naturally infected wild rodents.

BACKGROUND: Tick-borne encephalitis virus (TBEV) can cause severe neurological disease in humans. Its geographical distribution is expanding in Western Europe with unresolved causes and spatial patterns, necessitating enhanced surveillance. Monitoring the virus in the environment is complicated, as it usually relies on destructive sampling of small rodents to test organs for TBEV, which in addition to ethical considerations also raises issues for long-term monitoring or longitudinal studies. Moreover, even when the virus is not detected in the blood or organs of the rodent, TBEV can still be transmitted from an infected tick to uninfected ticks feeding nearby. This is due to the ability of TBEV to replicate and migrate locally within the epidermis of small mammals, including those that do not appear to have systemic infection. This suggests that the virus may be detectable in skin biopsies, which has been confirmed in experimentally infected laboratory rodents, but it remains unknown if this sample type may be a viable alternative to destructively obtained samples in the monitoring of natural TBEV infection. Here we test ear tissue and dried blood spot (DBS) samples from rodents to determine whether TBEV-RNA can be detected in biological samples obtained non-destructively. METHODS: Rodents were live-trapped and sampled at three woodland areas in The Netherlands where presence of TBEV has previously been recorded. Ear tissue (n = 79) and DBSs (n = 112) were collected from a total of 117 individuals and were tested for TBEV-RNA by real-time RT-PCR. RESULTS: TBEV-RNA was detected in five rodents (4.3% of tested individuals), all of which had a TBEV-positive ear sample, while only two out of four of these individuals (for which a DBS was available) had a positive DBS. This equated to 6.3% of ear samples and 1.8% of DBSs testing positive for TBEV-RNA. CONCLUSIONS: We provide the first evidence to our knowledge that TBEV-RNA can be detected in samples obtained non-destructively from naturally infected wild rodents, providing a viable sampling alternative suitable for longitudinal surveillance of the virus.

Recovery of western black-legged tick and vertebrate populations after a destructive wildfire in an intensively-studied woodland in northern California.

Despite increasing severity and frequency of wildfires, knowledge about how fire impacts the ecology of tick-borne pathogens is limited. In 2018, the River Fire burned a forest in the far-western U.S.A. where the ecology of tick-borne pathogens had been studied for decades. Forest structure, avifauna, large and small mammals, lizards, ticks, and tick-borne pathogens (Anaplasma phagocytophilum, Borrelia burgdorferi, Borrelia miyamotoi) were assessed after the wildfire in 2019 and 2020. Burning reduced canopy cover and eliminated the layer of thick leaf litter that hosted free-living ticks, which over time was replaced by forbs and grasses. Tick abundance and the vertebrate host community changed dramatically. Avian species adapted to cavity nesting became most prevalent, while the number of foliage-foraging species increased by 83% as vegetation regenerated. Nine mammalian species were observed on camera traps, including sentinel (black-tailed jackrabbits) and reservoir hosts (western gray squirrels) of B. burgdorferi. One Peromyscus sp. mouse was captured in 2019 but by 2020, numbers were rebounding (n=37), although tick infestations on rodents remained sparse (0.2/rodent). However, western fence lizards (n=19) hosted 8.6 ticks on average in 2020. Assays for pathogens found no B. miyamotoi in either questing or host-feeding ticks, A. phagocytophilum DNA in 4% (1/23) in 2019, and 17% (29/173) in 2020 for questing and host-feeding ticks combined, and B. burgdorferi DNA in just 1% of all ticks collected in 2020 (2/173). We conclude that a moderately severe wildfire can have dramatic impacts on the ecology of tick-borne pathogens, with changes posited to continue for multiple years.

Infection of wild-caught wood mice (Apodemus sylvaticus) and yellow-necked mice (A. flavicollis) with tick-borne encephalitis virus.

The distribution of tick-borne encephalitis virus (TBEV) is expanding to Western European countries, including the Netherlands, but the contribution of different rodent species to the transmission of TBEV is poorly understood. We investigated whether two species of wild rodents native to the Netherlands, the wood mouse Apodemus sylvaticus and the yellow-necked mouse Apodemus flavicollis, differ in their relative susceptibility to experimental infection with TBEV. Wild-caught individuals were inoculated subcutaneously with the classical European subtype of TBEV (Neudoerfl) or with TBEV-NL, a genetically divergent TBEV strain from the Netherlands. Mice were euthanised and necropsied between 3 and 21 days post-inoculation. None of the mice showed clinical signs or died during the experimental period. Nevertheless, TBEV RNA was detected up to 21 days in the blood of both mouse species and TBEV was also isolated from the brain of some mice. Moreover, no differences in infection rates between virus strains and mouse species were found in blood, spleen, or liver samples. Our results suggest that the wood mouse and the yellow-necked mouse may equally contribute to the transmission cycle of TBEV in the Netherlands. Future experimental infection studies that include feeding ticks will help elucidate the relative importance of viraemic transmission in the epidemiology of TBEV.

Will new ticks invade North America? How to identify future invaders.

Invasive tick species and the pathogens they transmit pose increasing threats to human and animal health around the world. Little attention has been paid to the characteristics enabling tick species to invade. Here we analyze examples of tick invasion events in North America to identify factors that facilitated the invasion. Commonalities among invasive ticks are that they thrive in anthropogenically modified habitats, feed on either domestic animals or wildlife occurring in high density, and can survive across a broad range of climatic conditions. Invasive tick species varied widely in life history and reproductive habits, suggesting that invasion occurs when multiple characteristics converge. The combination of potential characteristics leading to invasion, however, improves our ability to predict future invaders and inform surveillance.

Predicting the northward expansion of tropical lineage Rhipicephalus sanguineus sensu lato ticks in the United States and its implications for medical and veterinary health.

The tropical lineage within the Rhipicephalus sanguineus species complex is cause for growing concern in the U.S. based on its prominent role in creating and perpetuating multiple recently identified outbreaks of Rocky Mountain spotted fever in the southwestern United States and northern Mexico. This lineage is undergoing a northward range expansion in the United States, necessitating the need for enhanced surveillance for Rh. sanguineus. To inform more focused surveillance efforts we use species distribution models (SDMs) to predict current (2015-2019) and future (2021-2040) habitat for the tropical lineage. Models using the MaxEnt algorithm were informed using geolocations of ticks genetically confirmed to be of the tropical lineage, for which data on 23 climatic and ecological variables were extracted. Models predicted that suitability was optimal where temperatures are relatively warm and stable, and there is minimal precipitation. This translated into habitat being predicted along much of the coast of southern states including California, Texas, Louisiana, and Florida. Although the endophilic nature of tropical Rh. sanguineus somewhat violates the assumptions of SDMs, our models correctly predicted known locations of this tick and provide a starting point for increased surveillance efforts. Furthermore, we highlight the importance of using molecular methods to distinguish between ticks in the Rh. sanguineus species complex.

Prevalence and geographic distribution of Babesia conradae and detection of Babesia vogeli in free-ranging California coyotes (Canis latrans).

Babesia species are intraerythrocytic piroplasms that can result in disease characterized by hemolytic anemia and thrombocytopenia. Of the 5 species that are known to infect canids in the United States, Babesia conradae is most frequently diagnosed in California, and Babesia vogeli is prevalent in the US. Despite the recent re-emergence of B. conradae, the mechanism of transmission is not known. Coyotes (Canis latrans) have been a proposed reservoir of disease, and previous work has shown that dogs with known aggressive interactions with coyotes are at greater risk for infection. This study aimed to determine the prevalence of B. conradae in wild coyote populations in California to assess the viability of coyotes as a potential source of infection for domestic dogs. Four hundred and sixty-one splenic samples were obtained during post-mortem examination of coyote carcasses from Southern California, Fresno, and Hopland. Demographic data including age, sex, cause of death, and urbanity were collected for each coyote. DNA was extracted from samples and amplified using real-time PCR with primers specific for the B. conradae ITS-2 gene. The 18S gene was amplified and sequenced using conventional PCR primers specific to the Babesia genus from any coyotes positive for B. conradae. In total, 22 coyotes tested positive for B. conradae in Fresno (n = 15), Orange (n = 4), San Bernardino (n = 1), and Los Angeles counties (n = 1) with an overall prevalence of 4.8%. Coyotes from Fresno (P<.01) and rural coyotes (P<.01) were significantly more likely to be infected with B. conradae. Ten of 14 samples sequenced were 99-100% homologous to B. conradae, and 4 samples were 100% homologous with B. vogeli DNA indicating co-infection with both pathogens. This study demonstrates that coyotes can become infected and harbor B. conradae and B. vogeli and should be investigated as a possible source of infection in domestic dogs.

Detection and Isolation of Rickettsia tillamookensis (Rickettsiales: Rickettsiaceae) From Ixodes pacificus (Acari: Ixodidae) From Multiple Regions of California.

The western black-legged tick (Ixodes pacificus) is the most frequently identified human-biting tick species in the western United States and the principal vector of at least three recognized bacterial pathogens of humans. A potentially pathogenic Rickettsia species, first described in 1978 and recently characterized as a novel transitional group agent designated as Rickettsia tillamookensis, also exists among populations of I. pacificus, although the distribution and frequency of this agent are poorly known. We evaluated DNA extracts from 348 host-seeking I. pacificus nymphs collected from 9 locations in five California counties, and from 916 I. pacificus adults collected from 24 locations in 13 counties, by using a real-time PCR designed specifically to detect DNA of R. tillamookensis. DNA of R. tillamookensis was detected in 10 (2.9%) nymphs (95% CI: 1.6-5.2%) and 17 (1.9%) adults (95% CI: 1.2-3.0%) from 11 counties of northern California. Although site-specific infection rates varied greatly, frequencies of infection remained consistently low when aggregated by stage, sex, habitat type, or geographical region. Four novel isolates of R. tillamookensis were cultivated in Vero E6 cells from individual adult ticks collected from Alameda, Nevada, and Yolo counties. Four historical isolates, serotyped previously as 'Tillamook-like' strains over 40 yr ago, were revived from long-term storage in liquid nitrogen and confirmed subsequently by molecular methods as isolates of R. tillamookensis. The potential public health impact of R. tillamookensis requires further investigation.

Detection of Babesia odocoilei in Ixodes scapularis Ticks Collected in Southern Ontario, Canada.

Tick-borne zoonotic diseases have an economic and societal impact on the well-being of people worldwide. In the present study, a high frequency of Babesia odocoilei, a red blood cell parasite, was observed in the Huronia area of Ontario, Canada. Notably, 71% (15/21) blacklegged ticks, Ixodes scapularis, collected from canine and feline hosts were infected with B. odocoilei. Consistent with U.S. studies, 12.5% (4/32) of questing I. scapularis adults collected by flagging in various parts of southwestern Ontario were positive for B. odocoilei. Our data show that all B. odocoilei strains in the present study have consistent genetic identity, and match type strains in the GenBank database. The high incidence of B. odocoilei in the Huronia area indicates that this babesial infection is established, and is cycling enzootically in the natural environment. Our data confirm that B. odocoilei has wide distribution in southern Ontario.

Detection of Babesia odocoilei in Humans with Babesiosis Symptoms.

Human babesiosis is a life-threatening infectious disease that causes societal and economic impact worldwide. Several species of Babesia cause babesiosis in terrestrial vertebrates, including humans. A one-day clinic was held in Ontario, Canada, to see if a red blood cell parasite, which is present in blacklegged ticks, Ixodes scapularis, is present in humans. Based on PCR testing and DNA sequencing of the 18S rRNA gene, we unveiled B. odocoilei in two of 19 participants. DNA amplicons from these two patients are almost identical matches with the type strains of B. odocoilei in GenBank. In addition, the same two human subjects had the hallmark symptoms of human babesiosis, including night sweats, chills, fevers, and profound fatigue. Based on symptoms and molecular identification, we provide substantive evidence that B. odocoilei is pathogenic to humans. Dataset reveals that B. odocoilei serologically cross-reacts with Babesia duncani. Clinicians must realize that there are more than two Babesia spp. in North America that cause human babesiosis. This discovery signifies the first report of B. odocoilei causing human babesiosis.

Response of small mammal and tick communities to a catastrophic wildfire and implications for tick-borne pathogens.

Through their potentially devastating impacts on the environment, wildfires may impact pathogen, vector, and host interactions, leading to changing risks of vector-borne disease in humans and other animals. Despite established risks for tick-borne disease and increasing frequency and severity of wildfires in the United States, impacts of wildfire on ticks and tick-borne pathogens are understudied. In 2015, the large Wragg fire extensively burned a long-term field site at Stebbins Cold Canyon University of California Reserve (CC). We characterized the tick, reservoir host and pathogen community over a two-year period after the burn, comparing our findings to pre-fire data and to data from Quail Ridge Reserve (QR), a nearby unburned site. After the fire, there were 5.5 times more rodent, primarily Peromyscus spp., captures at CC than QR (compared to 3.5 times more pre-fire). There were significantly fewer dusky-footed woodrats (Neotoma fuscipes) at both sites post-fire, likely due to drought but not fire. Pre-fire tick infestation prevalence on rodents was comparable across sites (12.5% at CC and 9.9% at QR) and remained low at CC post-fire (13.7%) but was significantly higher at QR (48.0%), suggesting that ticks or their habitat were destroyed during the burn. Normalized difference vegetation indices documented a 16-fold loss of vegetation post- compared to pre-fire at CC; loss of vegetation and direct impacts on fauna are likely the main drivers of the post-fire differences in ticks we saw at CC. These data contribute to our understanding of tick-associated disease risks in our increasingly disturbed landscapes.

Detection of Babesia odocoilei in Ixodes scapularis Ticks Collected from Songbirds in Ontario and Quebec, Canada.

Songbirds widely disperse ticks that carry a diversity of pathogens, some of which are pathogenic to humans. Among ticks commonly removed from songbirds, the blacklegged tick, Ixodes scapularis, can harbor any combination of nine zoonotic pathogens, including Babesia species. From May through September 2019, a total 157 ticks were collected from 93 songbirds of 29 species in the Canadian provinces of Ontario and Québec. PCR testing for the 18S gene of Babesia species detected Babesia odocoilei in 12.63% of I. scapularis nymphs parasitizing songbirds in Ontario and Québec; none of the relatively small numbers of Ixodes muris, Ixodes brunneus, or Haemaphysalis leporispalustris were PCR-positive. For ticks at each site, the prevalence of B. odocoilei was 16.67% in Ontario and 8.89% and 5.26% in Québec. Of 31 live, engorged I. scapularis larvae and nymphs held to molt, 25 ticks completed the molt; five of these molted ticks were positive for B. odocoilei. PCR-positive ticks were collected from six bird species-namely, Common Yellowthroat, Swainson's Thrush, Veery, House Wren, Baltimore Oriole, and American Robin. Phylogenetic analysis documented the close relationship of B. odocoilei to Babesia canis canis and Babesia divergens, the latter a known pathogen to humans. For the first time in Canada, we confirm the transstadial passage of B. odocoilei in I. scapularis molting from larvae to nymphs. A novel host record reveals I. scapularis on a Palm Warbler. Our findings show that B. odocoilei is present in all mobile life stages of I. scapularis, and it is widely dispersed by songbirds in Ontario and Québec.

Monitoring of Nesting Songbirds Detects Established Population of Blacklegged Ticks and Associated Lyme Disease Endemic Area in Canada.

This study provides a novel method of documenting established populations of bird-feeding ticks. Single populations of the blacklegged tick, Ixodes scapularis, and the rabbit tick, Haemaphysalis leporispalustris, were revealed in southwestern Québec, Canada. Blacklegged tick nymphs and, similarly, larval and nymphal rabbit ticks were tested for the Lyme disease bacterium, Borrelia burgdorferi sensu lato (Bbsl), using PCR and the flagellin (flaB) gene, and 14 (42%) of 33 of blacklegged tick nymphs tested were positive. In contrast, larval and nymphal H. leporsipalustris ticks were negative for Bbsl. The occurrence of Bbsl in I. scapularis nymphs brings to light the presence of a Lyme disease endemic area at this songbird nesting locality. Because our findings denote that this area is a Lyme disease endemic area, and I. scapularis is a human-biting tick, local residents and outdoor workers must take preventive measures to avoid tick bites. Furthermore, local healthcare practitioners must include Lyme disease in their differential diagnosis.

Borrelia burgdorferi and Anaplasma phagocytophilum Genospecies in Northern California.

The sensu lato (s.l.) complexes of Borrelia burgdorferi and Anaplasma phagocytophilum include pathogenic genospecies each with distinct ecologies in northern California, yet, most work conflates the genospecies of each pathogen into one sensu lato species. Detailed understanding of the differences in geographic distributions and ecology among genospecies is lacking. We aimed to evaluate whether two B. burgdorferi and two A. phagocytophilum genospecies in high-risk locations in coastal northern California were spatially clustered and if presence of a particular genospecies was associated with geographical site, host species, or other demographic or ecological variables. DNA sequencing was performed to differentiate genospecies of Borreliae and Anaplasma from PCR-positive dusky-footed woodrats (Neotoma fuscipes) and sciurids (chipmunks, Tamias spp., and Douglas squirrels, Tamiasciurus douglasii) at four sites in northwestern California. Logistic regression was performed to assess associations of genospecies with the predictor variables host species, host sex, site, season, and year. Spatial clustering was assessed using a Poisson spatial scan statistic in SaTScan. Host species was a significant predictor for Borrelia bissettiae, B. burgdorferi sensu stricto (s.s.), A. phagocytophilum s.s., and the DU1 Anaplasma genospecies. Woodrats were significantly more likely to be PCR-positive for B. bissettiae and A. phagocytophilum DU1 genospecies, while A. phagocytophilum s.s. and B. burgdorferi s.s. were significantly associated with sciurids. We report a single Borrelia lanei in an Allen's chipmunk (Tamias senex) from the Hoopa Valley Tribal Reservation. A significant spatial cluster of A. phagocytophilum s.s. was detected at Hendy Woods State Park in Mendocino County. These results highlight the need to better understand genospecies partitioning according to host species to further assess human risks, aid in future surveillance, and inform targeted research.

Modeling Potential Habitat for Amblyomma Tick Species in California.

The Amblyomma genus of ticks comprises species that are aggressive human biters and vectors of pathogens. Numerous species in the genus are undergoing rapid range expansion. Amblyomma ticks have occasionally been introduced into California, but as yet, no established populations have been reported in the state. Because California has high ecological diversity and is a transport hub for potentially parasitized humans and animals, the risk of future Amblyomma establishment may be high. We used ecological niche modeling to predict areas in California suitable for four tick species that pose high risk to humans: Amblyomma americanum, Amblyomma maculatum, Amblyomma cajennense and Amblyomma mixtum. We collected presence data in the Americas for each species from the published literature and online databases. Twenty-three climatic and ecological variables were used in a MaxEnt algorithm to predict the distribution of each species. The minimum temperature of the coldest month was an important predictor for all four species due to high mortality of Amblyomma at low temperatures. Areas in California appear to be ecologically suitable for A. americanum, A. maculatum, and A. cajennense, but not A. mixtum. These findings could inform targeted surveillance prior to an invasion event, to allow mitigation actions to be quickly implemented.

Human Seroprevalence of Tick-Borne Anaplasma phagocytophilum, Borrelia burgdorferi, and Rickettsia Species in Northern California.

There is a paucity of data on human exposure to tick-borne pathogens in the western United States. This study reports prevalence of antibodies against three clinically important tick-borne pathogens (Borrelia burgdorferi, Anaplasma phagocytophilum, and Rickettsia spp.) among 249 people in five counties in northern California. Individuals from Humboldt County were recruited and answered a questionnaire to assess risk of exposure to tick-borne pathogens. Samples from other counties were obtained from a blood bank and were anonymized. Seventeen (6.8%) samples were seropositive for antibodies against at least one pathogen: five for A. phagocytophilum, eight for B. burgdorferi, and four for Rickettsia spp. Women and people aged 26-35 had higher seroprevalence compared to other demographic groups. Santa Cruz County had no seropositive individuals, northern Central Valley counties had three seropositive individuals (all against A. phagocytophilum), and Humboldt County had 14 (all three pathogens), a significant, four-fold elevated risk of exposure. The Humboldt County questionnaire revealed that a bird feeder in the yard was statistically associated with exposure to ticks, and lifetime number of tick bites was associated with increasing age, time watching wildlife, and time hiking. Three-quarters of respondents were concerned about tick-associated disease, 81.0% reported experiencing tick bites, and 39.0% of those bitten reported a tick-borne disease symptom, including skin lesions (76.4%), muscle aches (49.1%), joint pain (25.5%), or fever (23.6%). Despite high levels of concern, many individuals who had been bitten by a tick were not tested for a tick-borne pathogen, including those with consistent symptoms. We highlight the need for further research and dissemination of information to residents and physicians in Northern California regarding tick-associated disease, so that appropriate medical attention can be rapidly sought and administered.

Sometimes Scientists Get the Flu. Wrong !

In an international research environment, accurate communication is vital. However, the scientific literature does not always utilise consistent terminology and the misuse of some expressions in epidemiology is rife. We encourage the correct terms to be used appropriately to avoid confusion between scientists, policy makers, and members of the public.

Network analysis of gut microbiota literature: an overview of the research landscape in non-human animal studies.

A wealth of human studies have demonstrated the importance of gut microbiota to health. Research on non-human animal gut microbiota is now increasing, but what insight does it provide? We reviewed 650 publications from this burgeoning field (2009-2016) and determined that animals driving this research were predominantly 'domestic' (48.2%), followed by 'model' (37.5%), with least studies on 'wild' (14.3%) animals. Domestic studies largely experimentally perturbed microbiota (81.8%) and studied mammals (47.9%), often to improve animal productivity. Perturbation was also frequently applied to model animals (87.7%), mainly mammals (88.1%), for forward translation of outcomes to human health. In contrast, wild animals largely characterised natural, unperturbed microbiota (79.6%), particularly in pest or pathogen vectoring insects (42.5%). We used network analyses to compare the research foci of each animal group: 'diet' was the main focus in all three, but to different ends: to enhance animal production (domestic), to study non-infectious diseases (model), or to understand microbiota composition (wild). Network metrics quantified model animal studies as the most interdisciplinary, while wild animals incorporated the fewest disciplines. Overall, animal studies, especially model and domestic, cover a broad array of research. Wild animals, however, are the least investigated, but offer under-exploited opportunities to study 'real-life' microbiota.

Parasite community dynamics in an invasive vole - From focal introduction to wave front.

Multiple parasite species simultaneously infecting a host can interact with one another, which has the potential to influence host-parasite interactions. Invasive species typically lose members of their parasite community during the invasion process. Not only do the founding population escape their parasites, but the rapid range expansion of invaders once in the invaded range can lead to additional stochastic loss of parasites. As such, parasite community dynamics may change along an invasion gradient, with consequences for host invasion success. Here, we use the bank vole, Myodes glareolus, introduced as a small founding population at a point source in the Republic of Ireland in c.1920's and its ecto- and endoparasites to ask: i) how does the parasite community vary across an invasion gradient, and ii) are parasite community associations driven by host traits and/or distance from the point of host introduction? We sampled the parasite community of M. glareolus at the proposed focal site of introduction, at mid-wave and the invasion front, and used a parasite interactivity index and statistical models to determine the potential for the parasite community to interact. Bank voles harboured up to six different parasite taxa, with a significantly higher parasite interactivity index at the foci of introduction (z = 2.33, p = 0.02) than elsewhere, suggesting the most established parasite community has greater opportunities to interact. All but one of four synergistic parasite community associations were driven by host traits; sex and body mass. The remaining parasite-parasite associations occurred at the mid-point of the invasion wave, suggesting that specific parasite-parasite interactions are not mediated by distance from a focal point of host introduction. We propose that host traits rather than location along an invasion gradient are more likely to determine parasite-parasite interactions in the invasive bank vole.

Global change, parasite transmission and disease control: lessons from ecology.

Parasitic infections are ubiquitous in wildlife, livestock and human populations, and healthy ecosystems are often parasite rich. Yet, their negative impacts can be extreme. Understanding how both anticipated and cryptic changes in a system might affect parasite transmission at an individual, local and global level is critical for sustainable control in humans and livestock. Here we highlight and synthesize evidence regarding potential effects of 'system changes' (both climatic and anthropogenic) on parasite transmission from wild host-parasite systems. Such information could inform more efficient and sustainable parasite control programmes in domestic animals or humans. Many examples from diverse terrestrial and aquatic natural systems show how abiotic and biotic factors affected by system changes can interact additively, multiplicatively or antagonistically to influence parasite transmission, including through altered habitat structure, biodiversity, host demographics and evolution. Despite this, few studies of managed systems explicitly consider these higher-order interactions, or the subsequent effects of parasite evolution, which can conceal or exaggerate measured impacts of control actions. We call for a more integrated approach to investigating transmission dynamics, which recognizes these complexities and makes use of new technologies for data capture and monitoring, and to support robust predictions of altered parasite dynamics in a rapidly changing world.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'.