Tularemia and the Battle to Protect Against It

When we think of biological threats and bioterrorism, it’s easy to imagine diseases like smallpox, anthrax, Ebola, etc. Tularemia, however, is often forgotten as a disease that poses both a public health threat and application as a biological weapon.

Its classification as a Category A agent makes the bacterium that causes tularemia, Francisella tularensis (F. tularensis), particularly challenging. Its ability to spread through both animal/vector exposures and through occupational hazards makes it unique. Tularemia is highly infectious and can spread through tick or deer fly bites, handling of infected animals, or inhalation of dust or aerosols that are contaminated. The distribution of cases mirrors that of the vectors and animals F. tularensis inhabits, which reflect profound changes to the environment through globalization, mass migration, and industrialization (ie, flooding, mild winters, abandoned housing, etc.). In fact, several state-sponsored programs have studied and utilized F. tularensis in their offensive bioweapons programs in the past. Although these offensive programs have vanished, there is still a concern for its use as a biological weapon by non-state actors or for a potential biosafety failure that would result in accidental infection in a laboratory setting.

There have also been occupational exposures due to aerosol-generating practices or laboratory safety mishaps that have occurred, which is somewhat unique to tularemia. Although laboratory accidents have occurred, the natural occurrence of the disease in the environment makes the occupational exposures particularly unique. Landscape work or farming is such a risk factor that even disease surveillance involves questions involving such work for potential cases.

Naturally-occurring tularemia infections tend to follow the distribution of its animal and arthropod vectors, thus cases are seen in Martha’s Vineyard, the south-central United States, the Pacific Northwest, etc. A 2003 study evaluated occupational exposure to the infection in landscapers in Martha’s Vineyard, Massachusetts, and found that not only were many workers seropositive, but those who were seropositive tended to use power blowers and weed-whackers and worked more hours than those who were negative. The US Centers for Disease Control and Prevention (CDC) monitor cases of the disease each year and reported 314 cases within the United States in 2015 and 180 cases in 2014. (A map of 2015 reported cases can be found here.)

Because tularemia infections can occur naturally, surveillance and response efforts against the infection are critical. Antibiotics like streptomycin and doxycycline can treat the bacterial infection; however, the disease is uncommon and has non-specific symptoms, it can pose diagnostic challenges for clinicians. According to the CDC, the only prevention strategy is to reduce exposure as a vaccine is not generally available in the United States and is under review by the US Food and Drug Administration. There have been considerable efforts to develop an effective and available vaccine for the disease; however, such attempts have been costly and difficult.

Appili Therapeutics is one company that is making progress towards a tularemia vaccine. They recently signed a license agreement with the National Research Council of Canada to develop ATI-1701, a vaccine to protect against F. tularensis. Partially funded by Defense Threat Reduction Agency, the hopes are to conduct pre-clinical and clinical testing and roll out this preventative measure as soon as possible.

Highly infectious diseases like tularemia pose unique threats to global health security, especially as zoonotic diseases that are susceptible to environmental and social influencers. Prevention efforts through vaccination, rapid diagnosis, and stronger surveillance will be critical as populations grow and encroach on nature.