Tick transmission of toxoplasmosis

ABSTRACT

Introduction: Infection with Toxoplasma gondii (T. gondii) causes the disease toxoplasmosis in humans and animals. Oral transmission alone may not explain the widespread distribution of this parasite over large species of host animals and geographic areas.

Areas covered: Limited studies indicate the potential role of ticks in the distribution of T. gondii. The possibility of transmission of T. gondii has been demonstrated in Dermacentor variabilis, Dermacentor andersoni, Amblyomma americanum, Dermacentor reticulatus, Ixodes ricinus, Ixodes amblyomma, Amblyomma cajennense, Ornithodorus moubata and Haemaphysalis longicornis. Tick transmission of T. gondii, spread of ticks and pathogens by migratory birds and presence in the United States (US) of tick vectors of human and animal disease like Haemaphysalis longicornis indigenous to other parts of the world provide a possible mechanism for the widespread distribution of T. gondii, and a potentially expanding disease threat.

Expert opinion: The evidence indicates that T. gondii is potentially an unrecognized tick-borne pathogen spreading toxoplasmosis, and that clinicians might consider toxoplasmosis in the differential diagnosis of tickborne diseases.

KEYWORDS:

• Tick
• tick borne disease
• Toxoplasma gondii
• toxoplasmosis

1. Introduction

1.1. Widespread distribution of toxoplasmosis

Toxoplasmosis is the disease in humans caused by infection with the Apicomplexan parasite Toxoplasma gondii (T. gondii) [1]. T. gondii is prevalent in most areas of the world [2] and is one of the most prevalent infections in humans, estimated to be 30–50% of the world population [3]. In the United States (US), more than 40 million people carry the parasite, and the Centers For Disease Control (CDC) advises that the infection in humans and animals may be for a lifetime [4].

Infection can be asymptomatic in humans but it can also cause significant disease in congenitally infected infants, immunodeficient patients and occasionally, in immunocompetent individuals. More recent studies have revealed an association with psychiatric disorders, such as schizophrenia and bipolar disorder [5,6] as well as neurologic disease, such as Alzheimer’s [7]. T. gondii is also a veterinary problem, causing illness in domestic and wild animals [8].

1.2. Transmission of T. gondii

Toxoplasmosis is thought to be acquired by the transmission of T. gondii from the definitive to intermediate hosts, from intermediate to definitive hosts, as well as between similar definitive and between similar intermediate hosts. Intermediate hosts are all warm-blooded animals (mammals and birds), including humans. Definitive hosts are members of the family Felidae, for example, domestic cats [2]. Humans most commonly acquire toxoplasmosis by ingestion of T. gondii cysts in infected meat or by the ingestion of sporulated oocysts from water, soil or food contaminated indirectly from feline feces, or less frequently, directly from feline feces [2,9]. In the US, T. gondii is second only to Salmonella as a domestically acquired foodborne illness resulting in death [10]. Transmission by blood transfusion [11] and organ transplantation [12] has also been reported. Little is known about the relative importance of horizontal transmission of T. gondii between different host species or the epidemiologic impact of the different sources causing infection or disease.

Oral transmission alone may not explain the common occurrence of this parasite in a variety of hosts, such as herbivorous mammals, that are unlikely to contract primary infection orally with meat or cat feces [13]. Studies of risk factors for human infection [14] demonstrated that 31% of patients transmitting toxoplasmosis congenitally to their children demonstrated none of the common risk factors for T. gondii exposure: ownership of a pet cat was not a significant risk factor. Furthermore, a study from Switzerland to determine the prevalence of oocyst shedding by cats and to assess the levels of infection with T. gondii in meat-producing animals demonstrated a wide prevalence of T. gondii – low in sheep and pigs at 0.1–4.8% and high in cattle at 2.8%-7.2% but the prevalence of T. gondii in feline feces was only 0.4% [15]. However, soil is recognized as an important source of T. gondii infection in humans [16]: the oocyst stage of T. gondii shed in the millions by an infected cat, their large distribution in human environments, and their high viability in the soil to survive for long periods likely contributes to the high prevalence of toxoplasmosis.

The purpose of this paper is to review the limited studies available which indicate the potential role of ticks in the distribution of T. gondii and to encourage future investigations.

2. Role of ticks in the spread of T. gondii

The role of ticks in transmission of T. gondii has been considered [13,17–19]. The number of reports of tickborne bacterial and protozoan diseases in the US and territories from 2004 to 2016 totaled 491,671 [20]. However, the CDC announced that the number of cases of Lyme disease is under-reported annually by at least 10-fold. Only about 30,000 cases are reported, but the CDC says that it is more likely 300,000 new cases annually [21]. Ticks, which are blood-sucking arthropods, transmit pathogens that cause disease through the process of feeding, and thereby may contribute to the spread of T. gondii. Any intermediate host of T. gondii may serve as a source of blood for each stage of a tick, increasing infected populations among all intermediate host species, and theoretically creating the possibility of human infection by the transmission of T. gondii forms in blood by transfusion [22]. This may help explain the widespread distribution of this parasite over a large spectrum of animal species and large geographic areas [23].

Approximately 865 species of ticks exist worldwide [24]. Of the many different tick species found throughout the world, only a select few bite and transmit the disease to people. Of the ticks that bite people, different species of ticks transmit different diseases [25]. Human-biting ticks in the US include American dog tick (Dermacentor variabilis), Blacklegged deer tick (Ixodes scapularis), Brown dog tick (Rhipicephalus sanguineus), Gulf Coast tick (Amblyomma maculatum), Lone star tick (Amblyomma americanum), Rocky Mountain wood tick (Dermacentor andersoni), and Western blacklegged tick (Ixodes pacificus). Ticks can ingest many kinds of microorganisms while feeding on blood from hosts; however, they may not be able to transmit all the microorganisms they ingest.

3. Ticks as a source of transmission of T. gondii

Early cases of human toxoplasmosis associated with tick bite have been described, although the evidence that the disease was transmitted by ticks was circumstantial [18,26,27]. In a summary of early studies on the possibility of transmission of T. gondii from 18 species of arthropods in the US to different host animals (rabbits, guinea-pigs, hamsters, rats, mice, voles, chicks and pigeons), Woke et al. [19] and Jacobs [28] concluded that toxoplasmas may be ingested by blood-sucking arthropods and may survive in them for a number of days, but evidence of transmission by bite was lacking. Havlik [29] in Poland reported results from the experimental transmission of T. gondii by Ornithodorus moubata in which toxoplasma survived in the ticks at least 23 days but the tick bite did not appear to transmit the infection.

However, three ticks, Dermacentor variabilis (American dog tick), Dermacentor andersoni (Rocky Mountain wood tick) and Amblyomma americanum (Lone star tick) did show apparent transmission in the laboratory [19]. Infection in the tick Dermacentor variabilis and Amblyomma americanum appears to have been acquired in the larva or nymph stages and to have been transmitted to hosts through feeding in the adult stage. Infection in Dermacentor andersoni appears to have been carried transovarial through the eggs from the infection as larva, nymphs or adults to all three stages of the succeeding generation and from the nymphs to hosts through the bite.

Since these early studies, there have been other reports that support the possibility of transmission of T. gondii by ticks:

• Dermacentor reticulatus (Ornate cow tick), a human-biting tick [30] – T. gondii DNA was detected in 0–16.7% of adult ticks from different localities in eastern Poland; All isolates of T. gondii belonged to the type I genotype [31].

• Ixodes ricinus (Castor bean tick) – a human-biting tick [32] – T. gondii DNA was detected in 2.8% of adult female ticks from the woodlands of eastern Poland [13], 12.7% of adult (the higher percentage was female) and nymphs from the woodlands of north-western Poland [33], and 64.9% of adult ticks (the higher percentage was female) and nymphs in Upper Silesia, Poland [34].

  • T. gondii DNA was also found in adults, nymphs, and larvae of Ixodes ricinus feeding on ponies and questing on vegetation in northwestern Poland [35]. T. gondii genotype one was detected in 4.5% of all ticks including 3.0% feeding ticks, 3.0% females, 2.7% males, 2.8% nymphs and 10.2% of questing ticks.

  • Transmission of T. gondii by nymphs of Ixodes ricinus was demonstrated experimentally and found microscopically the presence of tachyzoites and bradyzoites in the tissues of nymphs in Poland [17].

  • Genotyping of T. gondii DNA isolates from a Polish population of Ixodes ricinus detected genotype I [33,35] or I or II/III clonal type [33,36] or unique type [23,33].

• Ixodes amblyomma infected with T. gondii in the Republic of Chad [37].

• Amblyomma cajennense (Cayenne tick) – a human-biting tick [38] – T. gondii in a Brazilian study, and the author commented that the mechanism of transmission was thought to be through the bite [39].

• Haemaphysalis longicornis (Asian longhorned tick) – a human-biting tick [40] – T. gondii ticks in China demonstrated a high infection rate in adult (11.3%) and nymph (6%) ticks from the field; no infected larvae were found. T. gondii can survive and remain infective in the tick’s body for at least 15 days in contrast to the currently accepted belief that T. gondii infection is possible only in warm-blooded animals [41]. Peaks of infection in the ticks suggest parasite growth. However, blood-feeding of infected ticks did not transmit T. gondii to hosts but the ingestion of infected ticks was suggested to be a transmission route between the tick and the host.

  • Haemaphysalis longicornis was demonstrated to harbor T. gondii in Japan [42].

• Ornithodoros moubata (African hut tampan or Eyeless tampan tick) – a human-biting tick [38] infected with Toxoplasma that lived in nymphs up to 10 days and in adults for 2 days, although attempts to demonstrate transmission were unsuccessful [43]

4. Coinfection with various pathogens

Occurrence of co-infections with various pathogens creates a risk of increased severity of tick-borne disease [44]. Lyme disease, caused by Borrelia burgdorferi, has been reported to co-exist with toxoplasmosis [45]. Co-existence in ticks of T. gondii and Babesia microti was detected in 37% of total examined ticks in Upper Silesia, Poland [34]. In the study of Adamska and Skotarczak [35], co-infection mostly involved T. gondii and Borrelia burgdorferi. In another study, some of the most prevalent infection rates amongst six individual pathogens in Dermacentor reticulatis were found with T. gondii at 2.1% as compared to 1.6% with Borrelia burgdorferi. The infection rate with T. gondii was significantly greater in males. In this same study, 8.5% of the examined ticks demonstrated dual infections, the most common were dual infections with T. gondii (1.6%) and Borrelia burgdorferi (1.3%), the most noteworthy being an association with Anaplasma phagocytophilium and with Babesia spp [44]. Data from 46,000 subjects, 3440 tested for toxoplasmosis and 7800 for borreliosis, in an internet survey searched for the associations of these infections with 22 mental health disorders and other indices of impaired mental health [46]. Results obtained from the study suggested that toxoplasmosis has strong correlations with the rate of several mental health disorders but borreliosis showed only a weak association with major depression and with subjectively reported depressive and anxiety symptoms; these associations, however, seem to exist only in toxoplasmosis co-infected patients.

5. Geographic distribution, and role of migration and international travel in widespread distribution of T. gondii

Human exposure to T. gondii can exist in any geographic area of the world [47], especially with the increase in international travel – in 2017, 87,703,442 US citizens traveled overseas from the US compared to 80,226,167 in 2016 [48]. Travel outside the US has been identified as a risk factor for Toxoplasma infection in pregnant women [49] and travelers returning home from the tropics to the US with mononucleosis-like syndrome were reported to have toxoplasmosis in 22% of cases [50]. Tickborne diseases can also be acquired internationally [51], and travelers to high tick endemic areas may mistakenly expose themselves to T. gondii. In the US, tickborne diseases occur throughout the continental US but predominate in the eastern part of the country, in the Upper Midwest, and in areas along the Pacific Coast [20]. For comparison, the most identified cases of toxoplasmosis have been in the South, including South Atlantic and East and West South Central census regions [52,53].

The CDC [54] recently reported on the infestation in the US with the vector tick Haemaphysalis longicornis, a tick indigenous to Asia and Australia, and demonstrated in several studies to be infected with T. gondii [41,42]. From August 2017 through September 2018, vector and animal surveillance efforts resulted in 53 reports of Haemaphysalis longicornis in the US, including 38 (72%) from animal species (23 from domestic animals, 13 from wildlife, and 2 from humans). An additional 15 (28%) were identified from environmental sampling of grass or other vegetation. At present, there is no evidence that Haemaphysalis longicornis has transmitted pathogens to humans, domestic animals, or wildlife in the US; however, surveillance efforts did not include testing the ticks or hosts for pathogens. This species is a potential vector of a number of important agents of human and animal diseases in the US [41,55].

Birds play a central role in the ecology of tickborne pathogens by expanding tick populations and pathogens across vast distances and serve as reservoirs that maintain and amplify transmission locally [56]. Migratory birds have been linked to the spread of ticks and pathogens across the US [57] and thereby provide a mechanism of T. gondii transmission at great distances from where an infection was acquired. In the spring of 2013 and 2014, out of 3,844 birds from 85 different bird species from Central or South America, 3.6% were infected with ticks, either in the larva or nymph stage of development. The authors estimated that about 4 to 39 million ticks are brought to the US each year. Although the ticks were not tested for T. gondii, migratory birds introduce ticks to new habitats thus increasing the tick population across the country, and since the ticks found were all larvae or nymphs there was still a chance for them to become infected and spread the pathogen to future hosts. Viable T. gondii from five different genotypes have been detected in a migratory population of Canada geese [58]. However, the authors indicated that since the geese are ground feeding birds they could become infected by ingestion of sporulated T. gondii oocysts with feed and water.

6. Conclusion

The presence of T. gondii with the potential to cause both human and animal toxoplasmosis has been found in ticks. Lack of information and awareness of this potential problem, likely substantially underestimates T. gondii occurrence through ticks. The limited number of tick studies available indicate the potential for ticks to play a role in the transmission cycle of T. gondii – either directly through a blood meal, or indirectly through host ingestion of an infected tick. The ticks in which T. gondii have been found are predominantly human-biting ticks. Wojcik-Fatla et al. [31] suggested that for a three-host tick species like Dermacentor reticulatus, larvae feed on small mammals (rodents and insectivorous), nymphs feed on small mammals and medium-size animals (such as lagomorphs), and adults feed mostly on cattle and big wild ruminants (usually on elks). The finding of T. gondii DNA in unfed (questing) adult ticks suggests the possibility of vertical transmission of the pathogen, possibly transstadial or even transovarial. Woke et at [19] also found that Dermacentor andersoni appeared to pass T. gondii transovarial and transstadial. Vertical transmission could explain, at least in part, the common occurrence of toxoplasmosis in small mammals and big herbivorous animals, which are unlikely to contract the infection orally with meat or cat feces but could be infected by the bite of infected larvae and nymphs (in the case of small mammals) or adults (in the case of big herbivorous animals). It appears, too, that ticks can become infected when they ingest T. gondii which is present in mammalian blood and retain T. gondii following molting [41]. The limited studies available indicate the potential for transmission of the parasite to mammalian hosts upon ingestion of an infected tick.

Although some studies were not successful in isolating T. gondii from ticks collected in natural habitats or in experimental transmission [43,59–62]., the differences might be explained with a better understanding of the ecology of ticks and their association with hosts in the different environments, including changes in tick abundance according to climatic conditions, host factors, socio-demographic factors, and agricultural and wildlife management [63]. More information is needed on how T. gondii survives in natural settings. For elucidation of some of the other questions concerning the possible transmission of T. gondii by ticks, further studies are needed. It is unclear which stage(s) of life cycle of the tick might permit the transmission of T. gondii and how the life cycle of the parasite is expressed in the tick body. Given the recently documented occurrence of Haemaphysalis longicornis in the US, and the ability of T. gondii to survive in this tick species, further evaluation of the potential role of Haemaphysalis longicornis in the transmission of this disease agent among animal reservoirs, and possibly to humans, is warranted. Another area needing study is the determination of any correlation to Amblyomma americanum (Lonestar tick), which is prevalent in the South and Mid-Atlantic Regions – corresponding to the higher geographic location of toxoplasmosis in the US. Woke et al. [19] found that Amblyomma americanum appeared to maintain T. gondii for extended periods of time after infection.

7. Expert opinion

The steady rise of tick-borne diseases and their potential for causing morbidity and mortality in humans and animals [64] makes the discussion of T. gondii as a potential tick-transmitted disease significant. Noteworthy, too, is the discovery of T. gondii as a causative agent in some cases of neurological and psychiatric diseases, such as dementia, schizophrenia, bipolar disorder, and problems with anger and rage [65]. As these health conditions are also increasing, finding all reliable sources of T. gondii transmission is an important public health concern.

Ticks have been found to harbor hundreds of known pathogens, and it is widely believed that there are likely more tick-borne organisms, capable of causing human disease, yet to be discovered. Several tick species are currently known to harbor parasites, such as Babesia spp. and Theileria spp. The discovery that T. gondii is an unrecognized tick-borne pathogen helps to explain the widespread prevalence of the parasite and the presence of Toxoplasma in humans and animals without common risk factors, such as eating meat and cat ownership.

The expansion of human development and recreation into tick habitats, coupled with climate change and increased temperatures are resulting in increased human and tick interaction, even in the winter months. The CDC’s 2010 policy on climate change and public health sets forth priorities to prepare the US and the world for potential health issues associated with climate change [66]. Authors from the CDC’s National Centre for Emerging and Zoonotic Infectious Diseases cited in a 2010 paper that having a better understanding of the pathogens carried by vectors, such as ticks and mosquitoes, their ability to cause human disease, as well as their geographic distribution, needs to be a research priority in the quest to better prepare for climate change [66]. The authors noted the overwhelming task of identifying and cataloging such a diverse and lengthy list of pathogens, but stated this research is necessary to determine potential disease-endemic areas, the risks among habitat types, and the geographic shifts and changes in the distribution of pathogens associated with climate change. The research cited here evidencing T. gondii in three common ticks within the US should earn this parasite inclusion in tick-borne pathogen research.

The evidence for the potential role of the Lonestar tick (A. americanum) as a viable source of T. gondii should be a concern to researchers, clinicians and public health officials. Warmer temperatures have seen a rapid expansion of this species geographic habitat northward and westward in the US, with further expansion anticipated due to climate change [67]. It is also an extremely aggressive tick – just a hint of CO₂ exhaled by a potential host will cause these ticks to pursue the source. Further research is necessary to determine if the overlap of A. americanum distribution with the higher prevalence of T. gondii in the same geographic locale is coincidental or a possible indication of this aggressive tick’s role in spreading the disease.

Early research indicating the viability of T. gondii in ticks and the potential for tick transmission have been largely ignored. As research continues to evolve showing the role tick-borne diseases are playing in a myriad of disease states, it will be crucial for clinicians to have current data indicating whether they should consider toxoplasmosis in the differential diagnosis of tick-borne diseases.

Studies on the possible transmission of T. gondii from infected ticks to mammalian hosts are limited. Given the incidence of this parasite in the human population and the neurologic consequences of latent infection [68,69], it is important to identify if ticks play a role in the distribution of T. gondii. Among the questions to be answered by future research are which species of ticks are most likely to be viable transmitters, including the study of Ixodes scapularis (Blacklegged or Deer tick) – another tick with a rapidly expanding habitat within the US [70]. Early studies indicate a short lifespan of T. gondii within the tick. Newer studies to determine if the parasite has developed mechanisms to survive long-term inside these vectors are needed. Also, if ticks are firmly established as vectors of T. gondii, determining if the parasite can be transmitted to offspring transovarially will provide a better understanding of which life stage ticks are able to transmit the disease. Transmission time for ticks to convey the parasite to a host after attachment will also need to be established. Recent studies have found rapid transmission time after tick attachment for some tick-borne pathogens, such as Rickettsia rickettsii (Rocky Mountain Spotted Fever) in just 10 min of attachment if the tick has been feeding on prior hosts [71] and Powhassan virus in just 15 min of tick attachment [72].

Finally, if further research concludes that ticks play a potential or current role in the widespread prevalence of infection with T. gondii, a logical progressive step would be to make toxoplasmosis a reportable disease to increase awareness of the parasitic infection, as well as increase funding for research into reducing human exposure and developing more effective drugs for treatment.

Article highlights

• Oral transmission of Toxoplasma gondii (T. gondii) alone may not explain the widespread prevalence of human toxoplasmosis. Cases of toxoplasmosis associated with tick bite have been described. The potential role of ticks in the distribution of T. gondii is considered.

• Limited studies indicate the possibility of distribution of T. gondii from multiple species of human-biting ticks (Dermacentor reticulatus; Ixodes ricinus; Ixodes amblyomma; Amblyomma cajennense; Haemaphysalis longicornis; Ornithodoros moubata) to different host animals.

• Infection in the tick Dermacentor variabilis and Amblyomma americanum appears to have been acquired in the larva or nymph stages and to have been transmitted to hosts through feeding in the adult stage. Infection in Dermacentor andersoni appears to have been carried transovarial through the eggs from the infection as larva, nymphs or adults to all three stages of the succeeding generation and from the nymphs to hosts through the bite.

• In the United States, tickborne diseases occur throughout the continental US but predominate in the eastern part of the country, in the Upper Midwest, and in areas along the Pacific Coast. For comparison, the most identified cases of toxoplasmosis have been in the South, including South Atlantic and East and West South Central census regions.

• Tick distribution of T. gondii, occurrence of co-infections with various pathogens, spread of ticks and pathogens by migratory birds, and presence in the United States of tick vectors of human and animal disease like Haemaphysalis longicornis indigenous to other parts of the world, provide a possible mechanism for the widespread distribution of T. gondii, increased severity of tick-borne disease, and a potentially expanding disease threat.

Declaration of interest

R.R.Ben-Harari is an employee of Vyera Pharmaceuticals. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have received an honorarium for their review work, but have no other relevant financial relationships to disclose.

Additional information

Funding

This paper was not funded.