Francisella tularensis, Tularemia and Serological Diagnosis

Abstract

Tularemia is a zoonotic disease caused by the bacterium Francisella tularensis. The predominant sources, routes of infection, and clinical manifestations of human infections greatly vary according to the geographic area considered. Moreover, clinical suspicion of tularemia is often tricky because of the lack of specificity of the clinical manifestations. Because F. tularensis isolation is tedious and detection of its DNA usually requires removal of infected tissues, serological techniques are most often used for diagnostic confirmation. However, these techniques are varied and poorly standardized. The microagglutination test (MAT), the indirect immunofluorescence assay (IFA), and ELISA tests are currently the most frequently used techniques. These home-made and commercial tests are mainly used for tularemia diagnosis but also seroprevalence studies. ELISA tests detect specific antibodies within two weeks of disease evaluation, compared to 2-3 weeks for MAT and IFA. However, more false-positive results are usually reported with ELISA. The long-term persistence of anti-F. tularensis antibodies in patients with past tularemia infection hampers the diagnostic specificity of all these tests. Also, cross-reacting antibodies have been described (especially with Brucella and Yersinia species), although usually at a low level. The immunoblotting technique can highlight these serological cross-reactions. Tularemia remains an underdiagnosed disease in most endemic areas, and the clinical presentations of this disease are evolving. It is necessary to improve further speed and accuracy of tularemia diagnosis, as well as the standardization of diagnostic procedures.

Francisella and Antibodies

“…The IgG antibody isotype dominates during adaptive response to F. tularensis natural infection (i.e., from the second week after infection) in humans. Such a conclusion is supported by numerous studies, collectively discussed in a review by Maurin et al [63]. Among the IgG subclasses, the IgG2 subclass prevailed, having been diagnosed in 92.9% of patients with serologically confirmed tularemia.…”

“…Moreover, individual antibody isotypes and their specificities, which are easily detectable and available in serum and saliva, are of particular importance for such purposes because they may also demonstrate the history of tularemia outbreak (infection's early interval-IgM only, ongoing acute state-IgM and IgG, or infection occurred some time ago-IgG only) in the monitored area [51,[58][59][60][61][62]. There exist a substantial number of tests and technologies that enable tularemia-specific antibody monitoring, and that can be utilized in natural environmental studies [63].…”

An Indispensable Role for the MavE Effector of Legionella pneumophila in Lysosomal Evasion

“…Intracellular pathogens, whether cytosolic or intravacuolar within macrophages, have evolved idiosyncratic mechanisms to evade various innate defense processes avoiding degradation within macrophages (55)(56)(57)(58). These pathogenic mechanisms involve the injection or secretion of effectors into the host by various type I to IX translocation systems (59)(60)(61)(62) and are present in extracellular pathogens, such as Bordetella (63) as well. These effectors modulate various cellular processes as well as host metabolism to render the host cell suitable as a proliferative nutrient-rich niche (55,(64)(65)(66)(67)(68)(69)(70).…”

‘Unique does not mean impossible: infant presenting with complicated course of ulceroglandular tularemia.’

“…The diagnosis of tularemia is mainly based on clinical manifestations, epidemiological data together with a positive serological test [ 9 ]. ELISA and western Blot show high sensitivity and specificity [ 4 ].…”