Early Diagnosis of Tularemia by Flow Cytometry, Czech Republic, 2003–2015

We retrospectively assessed the utility of a flow cytometry–based test quantifying the percentage of CD3+ T cells with the CD4–/CD8– phenotype for predicting tularemia diagnoses in 64 probable and confirmed tularemia patients treated during 2003–2015 and 342 controls with tularemia-like illnesses treated during 2012–2015 in the Czech Republic. The median percentage of CD3+/CD4–/CD8– T cells in peripheral blood was higher in tularemia patients (19%, 95% CI 17%–22%) than in controls (3%, 95% CI 2%–3%). When we used 8% as the cutoff, this test’s sensitivity was 0.953 and specificity 0.895 for distinguishing cases from controls. The CD3+/CD4–/CD8– T cells increased a median of 7 days before tularemia serologic test results became positive. This test supports early presumptive diagnosis of tularemia for clinically suspected cases 7–14 days before diagnosis can be confirmed by serologic testing in regions with low prevalences of tularemia-like illnesses.

[1]  Ö. Terzi,et al.  Predicting tularemia with clinical, laboratory and demographical findings in the ED. , 2016, The American journal of emergency medicine.

[2]  D. Yıldırım,et al.  Evaluation of tularaemia courses: a multicentre study from Turkey. , 2014, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[3]  I. Bank,et al.  Quantitative Peripheral Blood Perturbations of γδ T Cells in Human Disease and Their Clinical Implications , 2014, Clinical Reviews in Allergy & Immunology.

[4]  V. Vaillant,et al.  10 years of surveillance of human tularaemia in France. , 2014, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[5]  Eli Schwartz,et al.  Gamma delta T cells in non-immune patients during primary schistosomal infection , 2014, Immunity, inflammation and disease.

[6]  B. Onal,et al.  Tularemia: potential role of cytopathology in differential diagnosis of cervical lymphadenitis: Multicenter experience in 53 cases and literature review , 2014, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[7]  W. Weichert,et al.  Unmasked: when a clinically malignant disease turns out infectious. A rare case of tularemia. , 2013, International journal of surgical pathology.

[8]  P. Mead,et al.  Clinical recognition and management of tularemia in Missouri: a retrospective records review of 121 cases. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  J. Brion,et al.  Human tularemia in France, 2006-2010. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[10]  M. Tan,et al.  Impact of age, gender, and race on circulating γδ T cells. , 2010, Human immunology.

[11]  H. Akbulut,et al.  Gamma/delta T cells in patients with acute brucellosis , 2009, Clinical and Experimental Medicine.

[12]  A. Sjöstedt.  Tularemia: History, Epidemiology, Pathogen Physiology, and Clinical Manifestations , 2007, Annals of the New York Academy of Sciences.

[13]  N. Letvin,et al.  Vγ2Vδ2+ T cells and anti-microbial immune responses , 2003 .

[14]  E. Bäck,et al.  An outbreak of primary pneumonic tularemia. , 2002, The New England journal of medicine.

[15]  A. Tärnvik,et al.  Vγ9Vδ2 T Cells in Human Legionellosis , 2001, Clinical Diagnostic Laboratory Immunology.

[16]  J. Pérez-Castrillón,et al.  Tularemia epidemic in northwestern Spain: clinical description and therapeutic response. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  A. Lim,et al.  High frequency of circulating γδ T cells with dominance of the Vδ1 subset in a healthy population , 2000 .

[18]  A. Tärnvik,et al.  The proportion of circulating γδ T cells increases after the first week of onset of tularaemia and remains elevated for more than a year , 2000 .

[19]  A. Sjöstedt,et al.  Expansion of Vγ9Vδ2 T Cells Is Triggered byFrancisella tularensis-Derived Phosphoantigens in Tularemia but Not after Tularemia Vaccination , 1998, Infection and Immunity.

[20]  M. Zeitz,et al.  The Number and Proportion of Vϒ9Vδ2 T Cells Rise Significantly in the Peripheral Blood of Patients After the Onset of Acute Coxiella burnetii Infection , 1997 .

[21]  J. Grunewald,et al.  Different Percentages of Peripheral Blood γδ+ T Cells in Healthy Individuals from Different Areas of the World , 1996 .

[22]  C. Caldwell,et al.  Lymphocytosis of γ/δ T Cells in Human Ehrlichiosis , 1995 .

[23]  W. Boom,et al.  CD4+ alpha beta T cell and gamma delta T cell responses to Mycobacterium tuberculosis. Similarities and differences in Ag recognition, cytotoxic effector function, and cytokine production. , 1995, Journal of immunology.

[24]  P. Kragsbjerg,et al.  Detection of bacterial DNA in cerebrospinal fluid by an assay for simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and streptococci using a seminested PCR strategy , 1994, Journal of clinical microbiology.

[25]  K. Mendis,et al.  Transient increase in circulating gamma/delta T cells during Plasmodium vivax malarial paroxysms , 1994, The Journal of experimental medicine.

[26]  S. Reed,et al.  Antigen-reactive gamma delta T cells in human leishmaniasis. , 1993, Journal of Immunology.

[27]  R. Gerli,et al.  Lymphocytes bearing the γδ T cell receptor in acute Brucella melitensis infection , 1993 .

[28]  R. Gerli,et al.  Lymphocytes bearing the gamma delta T-cell receptor in acute toxoplasmosis. , 1992, Immunology.

[29]  H. Takada,et al.  Predominant activation and expansion of V gamma 9-bearing gamma delta T cells in vivo as well as in vitro in Salmonella infection. , 1992, The Journal of clinical investigation.

[30]  T. Sumida,et al.  Predominant expansion of V gamma 9/V delta 2 T cells in a tularemia patient , 1992, Infection and immunity.

[31]  M. Maurin,et al.  Tularaemia: clinical aspects in Europe. , 2016, The Lancet. Infectious diseases.

[32]  I. Selingerová,et al.  [Immunological Aspects in Oncology--Circulating γδ T Cells]. , 2015, Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti.

[33]  R. Evans.  European Centre for Disease Prevention and Control. , 2014, Nursing standard (Royal College of Nursing (Great Britain) : 1987).

[34]  Z. Černý.  Changes of the epidemiology and the clinical picture of tularemia in Southern Moravia (the Czech Republic) during the period 1936–1999 , 2004, European Journal of Epidemiology.

[35]  J. Pérez-Castrillón,et al.  An outbreak of primary pneumonic tularemia. , 2002, New England Journal of Medicine.

[36]  W. Youden,et al.  Index for rating diagnostic tests , 1950, Cancer.

[37]  G. Mccoy,et al.  Further Observations on a Plague-Like Disease of Rodents with a Preliminary Note on the Causative Agent, Bacterium Tularense , 1912 .