1. Introduction
Ticks (Class Arachnida; Order Acari) are widespread across the United States (US) and tens of thousands of tick-borne diseases are reported yearly in the US. Approximately 40 tick species blood feed on humans in the US [
1] and at least 11 of these species are known to transmit infectious agents [
2,
3,
4]. The Centers for Disease Control and Prevention recognizes the following tick-borne diseases and pathogens in the US: Anaplasmosis, babesiosis,
Borrelia miyamotoi disease, Colorado tick fever, ehrlichiosis, Heartland virus, Lyme disease, Powassan disease,
Rickettsia parkeri rickettsiosis, Rocky Mountain spotted fever, tick-borne relapsing fever, tick paralysis, tularemia, Q-fever, and 364D rickettsiosis [
4].
Numerous studies have documented tick exposure as an occupational health issue for forestry personnel and others working (e.g., agricultural industry, military) and/or participating in recreational activities (e.g., hunting, hiking) where tick exposure is common. A study in Germany showed evidence for previous infection of foresters for tick borne pathogens
Bartonella Strong,
Borrelia burgdorferi Johnson,
Coxiella burnetii Derrick,
Francisella tularensis McCoy and Chapin, and tick-borne encephalitis virus [
5]. The same study reported a high incidence (31%) of
Borrelia burgdorferi (the causative agent of Lyme disease) seropositivity in participants was related to these characteristics: (1) male; (2) ≥50 years old; (3) reported >50 tick bites; and (4) worked in the forest. A study in Poland also found high incidence (50%) of
Borrelia burgdorferi antibodies in forestry workers [
6]. A study in US National Park Service employees showed prior infections with tick-borne pathogens, such as
Bartonella henselae Regnery, spotted fever group rickettsiae, and
Anaplasma phagocytophilum Foggie [
7]. However, most studies, including the aforementioned studies, do not ask participants about how long ticks were attached before being discovered/removed. In order to develop strategies to prevent occupational and recreational exposure to ticks and tick-borne diseases, we must have improved knowledge and education of risk factors [
5]. This includes health education about the importance of removing ticks as quickly as possible to reduce the chance of pathogen exposure. A study in military personnel showed that health education increased self-awareness and removal of ticks and this reduced tick bites [
8]. Military personnel may be exposed to tick-infested areas for multiple days (unlike foresters and/or recreational exposure), hence, removal of ticks while in the field is essential to reduce attachment times that can lead to pathogen transmission by infectious ticks. Individuals can also use preventative measures, such as wearing permethrin-treated clothing and/or repellant, in order to minimize tick exposure risk. Studies have shown these types of practices can reduce the incidence of tick bites, hence, reducing the potential for pathogen exposure [
9,
10].
Pathogen transmission by ticks depends on a variety of factors including duration of feeding time, pathogen titer, and extent of tissue (e.g., gut, salivary glands) infection at the time of blood feeding. Some pathogens require a period of replication and/or expansion (in response to a blood meal) prior to transmission from a tick. Consequently, host infection may be prevented if the tick is removed within a critical period of time after attachment; i.e., the longer a tick remains attached, the higher the likelihood that an infectious pathogen dose is transmitted [
11,
12,
13]. Replication and/or expansion has been documented for bacterial pathogens causing Rocky Mountain spotted fever, anaplasmosis, Lyme disease, and babesiosis [
14]. Tick-borne viruses differ from bacteria in the duration of replication/expansion required (if any) and may be transmitted more rapidly than bacteria [
12,
14]. It is important to note that not all ticks can become infected with, and transmit, all pathogens. Non-competent ticks may be able to acquire a pathogen from a host during blood feeding, but may not be able to sustain the pathogen through molting, and/or be able to transmit the pathogen. Immune responses to pathogens may be greater in non-vector competent ticks compared to ticks that are competent vectors [
15,
16].
Our findings indicate that the duration of tick attachment to vertebrates required for transmission of pathogens (e.g., bacteria, viruses) varies, with most information derived from experimental studies conducted on rodents e.g., [
14,
17]. The few studies of humans have largely been clinical investigations of disease case patients, e.g., [
18,
19]. Engorgement indices (the ratio between total tick body length and scutum length (or width); the ratio between alloscutum width and scutum width) were calculated to determine the duration of feeding for
Ixodes scapularis Say [
20]. It is unknown whether these indices can be applied equally to all tick species. After 24 h of attachment to laboratory rabbits, engorgement indices increased steadily in
I. scapularis when assayed at 36, 48, and 60 h post-attachment [
20]. The total tick body length and alloscutal width increased with increased blood feeding attachment time, while scutal length and width remained the same. The same study showed that, based on the engorgement indices, most (64%) adult ticks submitted for pathogen testing (for a variety of pathogens, such as
Borrelia burgdorferi) by human bite victims had been attached for ≤36 h, while only 41% of nymphs were removed at the same time point.
Hard ticks (Arachnida: Acari: Ixodidae) can mate on (usually Metastriata) or off (usually Prostriata) the host [
21]. After attachment, the mated female hard tick will engorge to ca. 100–200 times her unfed weight (depending on tick species) in order to develop eggs and subsequently oviposit [
15,
22]. A virgin female tick usually feeds only until the critical weight (10 times her unfed weight) is achieved and may wait on a host until a male finds her and copulation takes place [
22]. If a virgin tick is removed prior to mating, she may continue blood feeding at a later time if she has not yet reached the critical weight [
22]. Once attached to a vertebrate host, a mated female hard tick feeds for four to 15 days to acquire enough blood to develop eggs [
22,
23]. There is an initial slow feeding phase (≥7 days in adults) where the hard tick increases in size by ca. 10 times (critical weight) (in virgin and mated females), followed by a rapid feeding phase (12–24 h) (in mated females only) [
22,
23]. Others have shown that the mating stimulus for the rapid feeding phase in females may be something the male inserts via spermatophore, but not necessarily sperm, as irradiated male sperm (sterile) have still been shown to stimulate rapid feeding in
Dermacentor variabilis Say [
24]. The virgin female tick does not feed to a level above the critical weight so she can (1) remain small and reduce the chances of being detected (and potentially removed by grooming) by the host, or (2) have the opportunity to reattach to another host to find a mate, if needed [
22].
Hard ticks secrete an adhesive “cement” composed of proteins during the first five to 30 min of attachment (during the slow feeding phase) that helps secure them to the host [
23,
25,
26]. Over time, additional layers of cement are secreted [
27]. Studies on tick-borne encephalitis virus have shown higher virus titers in the cement plug than in the tick body (e.g.,
Ixodes ricinus (L.),
Ixodes persulcatus Schulze), hence, even after a tick is removed, disease-causing pathogens may still be present in the host [
26]. Mouthparts of different tick genera differ in length (e.g., shorter mouthparts extending into the dermis and epidermis for
Dermacentor,
Haemophysalis, and
Rhipicephalus, compared to longer mouthparts extending more deeply into the dermis for
Amblyomma and
Ixodes) [
15]. The amount of pathogens in the mouthparts of the tick would be expected to vary between vector-pathogen systems, hence, leaving remnants of tick mouthparts in the body after removal may leave pathogens behind, and possibly result in secondary infection [
28]. However, if the tick and tissue surrounding the tick bite site are removed before pathogens (e.g., spirochetes) have had time to disperse, infection may be prevented [
29].
Soft ticks (Arachnida: Acari: Argasidae) mate off the host, tend to inhabit animal burrows, and require a shorter feeding time (ca. 30–60 min) to fully engorge than hard ticks [
15]. The weight of a blood-fed female soft tick is ca. five to 12 times her unfed weight [
30] and, unlike hard ticks, mating status does not influence the blood meal size [
22]. Based on documented differences in engorgement periods, pathogen transmission by soft ticks may occur more rapidly than via hard ticks. Others have shown a dose-dependent relationship for successful pathogen transmission demonstrated by simultaneous blood feeding by multiple soft ticks (e.g., three
Ornithodoros turicata Duges start transmitting
Borrelia turicatae to mice within 15–40 s (tick-borne relapsing fever)) [
31].
Here, we review some important pathogens of public health concern transmitted by hard and soft ticks and associated diseases with a focus on the US. For each disease, we investigated the known tick vectors and (if known), and the duration of tick attachment required for pathogen transmission.
4. Discussion
Unlike mosquito-borne viruses that rely solely on the transfer of infectious saliva for propagation in vertebrate hosts, hard and soft ticks can transmit pathogens (viruses, bacteria, protozoa) via saliva, regurgitation of gut contents, and also via the cement-like secretion (hard ticks) used to secure itself to the host [
26]. Tick-borne diseases are an important health threat that continues to impact public health worldwide. The impact of tick-borne pathogens may be more extensive than currently understood due to factors such as nonspecific symptoms experienced during other illnesses, lack of adequate surveillance systems, and climatic variables impacting tick and animal behaviors [
95,
96]. Furthermore, emerging and re-emerging tick-borne pathogens necessitate the push for further research in this area to protect public health.
For tick-pathogen systems where published data exists on duration of tick attachment times, variation was observed between different pathogens and most assessments were conducted on nonhuman vertebrates, such as rodents. For hard ticks, the duration of attachment required for transmission of the virus evaluated here was shorter (15–30 min-POWV) than for bacteria (4–96 h-multiple species evaluated), protozoan (7–18 days-Babesia microti), and neurotoxin (5–7 days). For soft ticks, we found information on the duration of attachment time (15 s–30 min) required for transmission of Borrelia turicata and this was a relatively short time period (similar to POWV transmission by hard ticks) that related to the nature of soft ticks to have brief blood feeding periods, compared to longer feeding periods required by hard ticks.
Most studies involve placing multiple ticks on multiple rodents, rather than a single tick on a single rodent, hence, adding further complexity to the comparison of transmission rates and duration of attachment time required for transmission between studies. Multiple ticks may be simultaneously delivering different pathogen doses to the host, therefore, in these cases, the host infection rate cannot be tied to one dose delivered by one tick. Furthermore, some studies assess the bacteremia or viremia in ticks that fed upon mice, but others determine only the status of infection in mice that were fed upon and not ticks. Rarely do studies determine the titer of both tick and host, making it difficult to make a connection between the pathogen dose delivered by the tick and the infection rate of the host. We expect further variation to exist in vector competence due to the pathogen dose transmitted by ticks to hosts, biological and/or environmental conditions, pathogen/vector/host species and population, age of victims, and other unidentified factors. In order to improve species- and population-specific risk assessments of pathogen transmission to humans and other animals, more focused experimentally-controlled vector competence research is needed for tick-borne pathogens. Laboratory experiments are not always an indication of field conditions; however, laboratory vector competence studies could provide a basis and starting point for field assessments of risk.
We could not find any published tick attachment time data for the following pathogens: Southern tick associated rash illness, Borrelia parkeri Davis, Coxiella burnetii, Ehrlichia chaffeensis Anderson, Ehrlichia ewingii Ewing, Ehrlichia muris Wen, Rickettsia 364D, Rickettsia montanensis Lackman, Rickettsia parkeri Lackman, and Colorado tick fever virus. Workers in outdoor occupations, such as forestry and the military, as well as those spending time outdoors participating in recreational activities, should be aware of the relationship between tick attachment time and the potential for pathogen transmission. Tick exposure does not always result in pathogen transmission and disease; however, the health threat exists and individuals should be aware of how to prevent and/or mitigate these risks.