Higher prevalence of IgA to
S. negevensis detected in the HD patients, in comparison with the RT patients and the healthy population, was unexpected.
S. negevensis is a ubiquitous microorganism and aquatic environments involved as source of infection for humans, because of the large diffusion of the natural protozoan hosts in water habitats. To our knowledge, few researchers investigated the occurrence of
Simkania in water environments, obtaining very different results in terms of frequency of detection [
16,
23]. Our recent investigation detected the occurrence of
S. negevensis in chlorinated water samples collected from swimming pool facilities, examining those classified as spa plants where a high water temperature (32–36 °C) was present [
17]. In addition, samples from domestic water supplies were tested.
S. negevensis was isolated in spa water and subsequently identified by PCR. Also the presence of
S. negevensis in swimming pool water seems much higher compared to that of Legionella which has never been isolated from samples of inlet and pool water. This is probably due to the higher resistance of
S. negevensis to the greater chlorine concentration in swimming pool waters, confirming that chlorine did not prevent, at the concentrations recommended for swimming pools, the survival and growth of Simkania. Moreover,
S. negevensis was detected both in cold and hot water samples of the domestic water systems, while
Legionella was isolated only from the hot water delivered from the showers. The HD patients represent obviously the cohort most exposed to water
. In the present investigation, it is surprising to note that
S. negevensis was isolated in all water samples collected, both before and after specific disinfection treatment of the HD fluid and that the forced continuous contact of the HD subjects with the treated water could be a constant source of infection. The similarity between the data of the second serum samples and the first samples collected from
S. negevensis positive patients could be due to this fact. The Italian National Society of Nephrology has promoted the development of specific Guidelines for dialysis fluids. An optimal water treatment system should include tap water pre-treatment and a double reverse osmosis process. Every component of the system, including the delivery of the treated water to the dialysis machines, should prevent microbiological contamination of the fluid. Regular chemical and microbiological tests and a regular disinfection of the system are necessary. Treated tap water used to prepare dialysis fluid should be within the limits suggested by the European Pharmacopoeia for the water treatment system inlet and the reverse osmosis outlet. In addition dialysate, concentrate and infusion fluids must comply with the specific Pharmacopoeia limits. Frequently analysis on microbiological purity in dialysis fluid is a fundamental pre-requisite for dialysis quality. All Dialysis Unit Care should aim, as a matter, of course, to obtain an “ultra-pure” dialysate (microbial count <0.1 UFC/mL, endotoxins <0.03 U/mL). The two hemodialysis centers of the present study follow the guidelines of the Italian Society of Nephrology [
24,
25]. Our findings, however, suggest that the water treatment system is not able to purify the tap water from the
S. negevensis contamination and that treated water used in hemodialysis may be involved as a possible source of
S. negevensis infection, thus explaining the higher prevalence of
S. negevensis in the HD patients in comparison with RT patients. Mostly important, the forced continuous contact of the HD subjects with S.
negevensis could represent one of the several factors, not fully known, implicated in the uremic inflammation. Inflammation and end-stage renal disease are already an old and intimately related couple. During the last decades, there has been much progress in elucidating the molecular mechanisms that lead to inflammatory reactions. Moreover, we have also learnt a lot concerning the characteristic inflammatory profile of the HD patients, which results from both retention of inflammatory mediators and increased tissue production. It is largely recognized that persistent inflammation can perturbate bone homeostasis, thus triggering vascular and arterial calcification, main predictors of cardiovascular mortality in HD population [
26,
27]. Plenty of data exist on the direct involvement of the HD procedure on inflammation: the interaction of circulating monocytes with non-biocompatible membranes, the blood contact with non-sterile dialysate solution [
28], the use of un-pure dialysate [
29], the extent of convective transport, and the frequency and duration of dialysis [
30] also may contribute to the inflammatory process. Even more recent studies have reported the possibility that infectious agents can trigger a cascade of biochemical and biological reactions, leading to inflammation. In particular, microorganisms, such as
Chlamydia pneumoniae, have been implicated as causative or contributory factors, being associated with atherosclerosis progression [
31‐
33]. Then S. negevensis, belonging to the family Simkaniaceae in the order Chlamydiales, could continously trigger the cascade of reactions, leading to systemic inflammation typical of HD population. Moreover,
S. negevensis, just because similarly to Chlamydiae, is sensitive to tetracyclines and macrolides while ampicillin, penicillin G, bacitracin, cyclosporine and fluoroquinolones are not active against the microorganism [
34]. The patients selected in the present study, in particular the HD patients, are generally treated with quinolone or cephalosporins as a non specific therapy in suspected infectious events (athero-venous fistula inflammation, suspect central venous catheter infection, non-specific gastric disorders, reported urinary tract disorders) since a susceptibility test indicating a specific therapy is rarely available in this infectious events. Therefore, our patients do not generally take a correct therapy for
S. negevensis. About clinical involvement of S.
negevensis infection, previous evidence indicates a possible role in respiratory tract infections and S
. negevensis DNA was found in cardiovascular system, in particular
S. negevensis genome sequences were amplified from sections of carotid artery tissue [
35]. Moreover, some recent data suggest that the microorganism could be involved in non-specific gastroenteric symptoms [
18]. In patients of the present study, detection of specific antibodies to
S. negevensis did not show any association with respiratory diseases, gastroenteric disorders and/or cardiovascular events.