Host Immunity and Francisella tularensis: A Review of Tularemia in Immunocompromised Patients

Abstract

Tularemia, caused by the bacterium Francisella tularensis, is an infrequent zoonotic infection, well known in immunocompetent (but poorly described in immunocompromised) patients. Although there is no clear literature data about the specific characteristics of this disease in immunocompromised patients, clinical reports seem to describe a different presentation of tularemia in these patients. Moreover, atypical clinical presentations added to the fastidiousness of pathogen identification seem to be responsible for a delayed diagnosis, leading to a” loss of chance” for immunocompromised patients. In this article, we first provide an overview of the host immune responses to Francisella infections and discuss how immunosuppressive therapies or diseases can lead to a higher susceptibility to tularemia. Then, we describe the particular clinical patterns of tularemia in immunocompromised patients from the literature. We also provide hints of an alternative diagnostic strategy regarding these patients. In conclusion, tularemia should be considered in immunocompromised patients presenting pulmonary symptoms or unexplained fever. Molecular techniques on pathological tissues might improve diagnosis with faster results.

The Brief Case: Suspicious Gram-Negative Coccobacilli—Francisella tularensis subsp. novicida Isolated from an Immunocompromised Patient

“…However, other clinical syndromes result when the bacterium penetrates other barriers, including the skin (ulceroglandular), the conjunctivae (oculoglandular), and the upper gastrointestinal tract (oropharyngeal) ( 1 ). Ulceroglandular disease is a frequent presentation of tularemia and is marked by ulceration at the inoculation site with satellite inflammatory lymphadenopathy ( 5 ). Oculoglandular and oropharyngeal forms present after conjunctival and pharyngeal inoculation, respectively ( 5 ).…”

“…Ulceroglandular disease is a frequent presentation of tularemia and is marked by ulceration at the inoculation site with satellite inflammatory lymphadenopathy ( 5 ). Oculoglandular and oropharyngeal forms present after conjunctival and pharyngeal inoculation, respectively ( 5 ). Typhoidal tularemia describes an acute febrile illness that cannot be readily classified as one of the aforementioned syndromes.…”

Pulmonary tularaemia in a female adolescent with inflammatory bowel disease receiving infliximab: Do not miss the diagnosis

“…According to the WHO guidelines, doxycycline, ciprofloxacin, streptomycin or gentamicin are among the first line of treatment. Bauhaud et al 1 reported combined antibiotic therapy in the case reports of immunocompromised patients. Clinical condition of our patient treated with ciprofloxacin deteriorated, and full recovery without complication was observed only after 2 weeks of doxycycline therapy.…”

“…Since the initial control of the infection requires the production of interleukin-12, interferon γ, and tumor necrosis factor-α (TNF-α) by phagocytic cells, patients treated with anti-TNF-α agents as in case of our patient are at particular risk of developing F. tularensis infection. 1 A metaanalysis in adult inflammatory bowel disease patients receiving TNFα inhibitors demonstrated a doubled risk of opportunistic infections with an increased risk of granulomatous infection, especially tuberculosis or other bacterial diseases (Nocardia), viral (varicella zoster virus, EBV, CMV), or mycotic (Pneumocystis jiroveci) related to inhibition of TNF-α. 2 Pulmonary tularaemia typically presents with fever, chest pain and cough with scant sputum production.…”

The potential roles of interleukin-25 in infectious diseases

“…The expression of IL-25 is regulated by pathogenic or commensal bacteria. Francisella tularensis (Ft) is a Gram-negative bacterium that causes tularemia (108). IL-25 strongly activates ILC2, which rapidly secretes IL-25 and results in a positive feed-back loop upon Ft infection, and the administration of IL-25 notably increases IgM production in mice; antibody-mediated depletion of ILC2 mainly supports the source of IL-5, which is required for IgM production; therefore, discovering the IL-25-ILC2-IL-5 axis is a novel strategy to improve vaccination depending on the IL-17RB signal pathway (109).…”