The Revenge of the Ticks!

While a group of dedicated researchers develop novel method to control ticks, these tiny arachnids take revenge by spreading further and infecting people and animals with the pathogens they transmit.

Ticks, these small arachnid ectoparasites, that exclusively feed on blood, are second only to mosquitoes as vectors of human and animal disease. Except for the driest places on the planet, they can find you anywhere in the world, even in the Arctic and the Antarctic.  They have a tremendous diversity of 900 species, and have been pestering mammals, birds, reptiles and amphibians since the age of the Dinosaurs!

They transmit a wide range of pathogens, both bacteria, viruses and protozoans, as well as toxins. In North America, as well as in the Northern Hemisphere in general, the most important such pathogen is undoubtedly Borrelia burgdorferi, which causes Lyme disease. Since the pathogen has been discovered in the 1970s, roughly 30,000 new cases have been reported annually, but estimates by the CDC indicate that there might be as much as 300,000 new infections every year, mostly in the Northeastern states and the Great Lakes region. In addition to Lyme disease, ticks in the United States can transmit a range of other less well-known diseases, such as Rocky Mountain Spotted Fever, tularemia, Powassan virus disease, erlichiosis, babeosis, anaplasmosis, tick-borne relapsing fever, Colorado tick fever, Heartland virus, and the newly discovered Bourbon virus

Ticks and tick-borne diseases represent a growing problem worldwide as well as in the United States. The Entomological Society of America has recently released a statement, advocating increased support and funding for research, education and outreach on ticks and tick-borne diseases. The statement states that a “recent confluence of environmental, ecological, sociological, and human demographic factors has created a near perfect storm leading to more ticks in more places throughout North America”. Since 1993 to 2012, the number of counties classified as high incidence for Lyme disease has increased by 320%, from 43 to 182. The geographic spread of Ixodes scapularis and Borrelia burgdorferi has been partly linked to climate change, as well as forest fragmentation and the replacement of red foxes by coyotes across the landscape. This year, there are an unusually high number of cases of tularemia, also called rabbit fever, caused by Franciscella tularensiensis, reported from Wyoming, South Dakota, Nebraska, and Colorado.

There is clearly a need for more effective, novel interventions to control ticks and tick-borne diseases. A recent feature article in Nature summarized the novel approaches being developed currently, as well as the challenges associated with them. Unfortunately, ticks have a number of characteristics that preclude the development of novel genetic methods similar to those that are being developed to control mosquitoes. First, both sexes of ticks need to take bloodmeals for their survival and development at all life stages, whereas in mosquitoes only adult females bite. Second, adult ticks move relatively short distances during their lifetime, while mosquitoes fly several hundred meters if needed. These make any interventions based on mass release of modified ticks for population or disease control impractical. Surprisingly, even commonly recommended preventive measures, such as to wear long pants and repellents and frequent tick checks, have not been thoroughly evaluated. Many previously tried interventions, such as pesticide applications and the controlling of deer, have had mixed success. The Lyme disease vaccine licensed for humans in 1998 was withdrawn in 2002 due to limited sales and complaints of potential side effects, and there hasn’t been an alternative vaccine licensed ever since. A new and improved vaccine has now completed safety trials, but it’s future is still uncertain.

One of the most exciting novel developments is an oral vaccine developed not for people, but for mice, invented by Maria Gomes-Solecki at the University of Tennessee Health Science Center. This vaccine works very similarly to the well accepted rabies vaccine, using pellets delicious to mice to distribute antigens to which the mice then develop antibodies. In the northeastern US,  white-footed mice (Peromyscus leucopus) are the most important reservoir of Borrelia burgdorferi. The idea is that by vaccinating them, we can control Lyme disease in these rodents and the ticks, and subsequently reduce transmission to people and pets. In a preliminary study conducted by the legendary Dr. Richard Ostfeld, the prevalence of infected black-legged ticks have dropped by 75%, even though only 28% of the mice in the study area developed protective levels of antibodies. Now her company, US Biologic is working on developing the technology further.

However, even if we can vaccinate white-footed mice to reduce Lyme disease transmission risk, ticks can still infect us with the plethora of pathogens listed above. However, if we could somehow vaccinate the host that ticks feed on against the ticks themselves, we could deal with all of them at the same time. However, in order to do this, we need to find an antigen in the ticks themselves that the hosts’ immune system can develop antibodies against. Fortunately, the tick’s saliva provides a number of such antigens, and these are currently used to develop such anti-tick vaccines. This strategy is also proposed by US Biologic to develop bait to control ticks in general. However, heightened immunity to tick saliva in general can be a double-edged sword, as that is exactly what’s behind the symptoms of tick-bite associated red meat allergy.

While all of these novel control methods are promising, their development is slow, with uncertain support and funding. In the meantime, ticks and the diseases they transmit are spreading further, taking a revenge on us by biting and infecting more and more people for every moment of delay in combating them.

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