Serological reactivity to Anaplasma phagocytophilum in neoehrlichiosis patients

Abstract

The tick-borne bacterium Candidatus (Ca.) Neoehrlichia (N.) mikurensis is a cause of “fever of unknown origin” because this strict intracellular pathogen escapes detection by routine blood cultures. Case reports suggest that neoehrlichiosis patients may display serological reactivity to Anaplasma (A.) phagocytophilum. Since Anaplasma serology is part of the diagnostic work-up of undetermined fever in European tick-exposed patients, we wanted to investigate (1) the prevalence of A. phagocytophilum seropositivity among neoehrlichiosis patients, (2) the frequency of misdiagnosed neoehrlichiosis patients among A. phagocytophilum seropositive patients, and (3) the frequency of A. phagocytophilum and Ca. N. mikurensis co-infections. Neoehrlichiosis patients (n = 18) were analyzed for A. phagocytophilum IgM and IgG serum antibodies by indirect immunofluorescence assay. Serum samples from suspected anaplasmosis patients (n = 101) were analyzed for bacterial DNA contents by singleplex PCR specific for A. phagocytophilum and Ca. N. mikurensis, respectively. One fifth of the neoehrlichiosis patients (4/18) were seropositive for IgM and/or IgG to A. phagocytophilum at the time of diagnosis. Among the patients with suspected anaplasmosis, 2% (2/101) were positive for Ca. N. mikurensis by PCR whereas none (0/101) had detectable A. phagocytophilum DNA in the serum. To conclude, patients with suspected anaplasmosis may in fact have neoehrlichiosis. We found no evidence of A. phagocytophilum and Ca. N. mikurensis co-infections in humans with suspected anaplasmosis or confirmed neoehrlichiosis.

Cultivation of the causative agent of human neoehrlichiosis from clinical isolates identifies vascular endothelium as a target of infection

“…This member of the family Anaplasmataceae is thought to be an obligate intracellular bacterium and consequently does not grow on cell-free culture media. The infection is often designated as “fever of uncertain origin” among immune-suppressed patients and any ensuing thromboembolic or vascular complications are misinterpreted as being age-related or due to other associated medical conditions, since the majority of patients are middle-aged or older with underlying diseases [6,11]. Currently, panbacterial or specific PCR of blood samples is the only means of diagnosis.…”

Asymptomatic-anaplasmosis confirmation using genetic and serological tests and possible coinfection with spotted fever group Rickettsia: a case report

“…Because the increase in the plasma concentration of antibodies in response to A. phagocytophilum proceeds slowly, a significant increase is not detectable in the acute phase. Furthermore, there are cases where rescreening for antibodies should be performed at~1 month after the original test [18,19]. In the anaplasmosis IFA, our patient tested negative on the first visit, but IgM seroconversion was confirmed in the follow-up tests on June 22nd and June 28th.…”

“…Unlike Borrelia burgdorferi, A. phagocytophilum and SFG Rickettsia get inoculated into a host within 2 to 6 h of attachment following a tick bite [16]. The serological diagnosis of an A. phagocytophilum infection can be confirmed when there is a four-fold increase in the antibody titer in convalescent-phase serum compared to that in acute-phase serum [17,18]. Because the increase in the plasma concentration of antibodies in response to A. phagocytophilum proceeds slowly, a significant increase is not detectable in the acute phase.…”

The Seroprevalence of Anaplasma phagocytophilum in global human populations: a systematic review and meta‐analysis

“…A major reason for heterogeneity in our review was the regional variation in A. phagocytophilum seroprevalence in Europe and America. Studies conducted in 13 European countries in this review (including Poland, Norway, the Czech Republic, Portugal, Sweden, Slovakia and Slovenia) had A. phagocytophilum seroprevalence estimates >10% (Chmielewska‐Badoraet al, 2012; Cisak et al, 2005; Cochez et al, 2011; Dvorakova Heroldova & Dvorackova, 2014; Henningsson et al, 2015; Hjetland et al, 2015; Kalinova, Halanova, Cislakova, & Juris, 2015; Kocianova et al, 2008; Rojko et al, 2006; Wass et al, 2018; Fingerle et al, 1997; Chochlakis, Papaeustathiou, Minadakis, Psaroulaki, & Tselentis, 2008; Zukiewicz‐Sobczak et al, 2014), with the highest estimate being 30.1%. In Europe, about 100 confirmed HGA cases have been described since its initial identification in Slovenia in 1997 (Petrovec et al, 1997).…”