Microbiological Challenges in the Diagnosis of Chronic Q Fever

Diagnosis of chronic Q fever is difficult. PCR and culture lack sensitivity; hence, diagnosis relies mainly on serologic tests using an immunofluorescence assay (IFA). Optimal phase I IgG cutoff titers are debated but are estimated to be between 1:800 and 1:1,600. In patients with proven, probable, or possible chronic Q fever, we studied phase I IgG antibody titers at the time of positive blood PCR, at diagnosis, and at peak levels during chronic Q fever. We evaluated 200 patients, of whom 93 (46.5%) had proven, 51 (25.5%) had probable, and 56 (28.0%) had possible chronic Q fever. Sixty-five percent of proven cases had positive Coxiella burnetii PCR results for blood, which was associated with high phase I IgG. Median phase I IgG titers at diagnosis and peak titers in patients with proven chronic Q fever were significantly higher than those for patients with probable and possible chronic Q fever. The positive predictive values for proven chronic Q fever, compared to possible chronic Q fever, at titers 1:1,024, 1:2,048, 1:4,096, and ≥1:8,192 were 62.2%, 66.7%, 76.5%, and ≥86.2%, respectively. However, sensitivity dropped to <60% when cutoff titers of ≥1:8,192 were used. Although our study demonstrated a strong association between high phase I IgG titers and proven chronic Q fever, increasing the current diagnostic phase I IgG cutoff to >1:1,024 is not recommended due to increased false-negative findings (sensitivity < 60%) and the high morbidity and mortality of untreated chronic Q fever. Our study emphasizes that serologic results are not diagnostic on their own but should always be interpreted in combination with clinical parameters.     

High Coxiella burnetii DNA Load in Serum during Acute Q Fever Is Associated with Progression to a Serologic Profile Indicative of Chronic Q Fever

PCR is very effective in diagnosing acute Q fever in the early stages of infection, when bacterial DNA is present in the bloodstream but antibodies have not yet developed. The objective of this study was to further analyze the diagnostic value of semiquantitative real-time PCR (qPCR) in diagnosing acute Q fever in an outbreak situation. At the Jeroen Bosch Hospital, in 2009, qPCR testing for Coxiella burnetii DNA was performed for 2,715 patients suspected of having acute Q fever (positive, n = 385; negative, n = 2,330). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the qPCR assay were calculated for patients with negative qPCR results with a follow-up sample obtained within 14 days (n = 305) and qPCR-positive patients with at least one follow-up sample (n = 369). The correctness of the qPCR result was based on immunofluorescence assay results for samples submitted for qPCR and follow-up testing. The sensitivity of the Q fever qPCR assay was 92.2%, specificity 98.9%, PPV 99.2%, and NPV 89.8%. Patients who later developed serologic profiles indicative of chronic Q fever infection had significantly higher C. burnetii DNA loads during the acute phase than did patients who did not (P < 0.001). qPCR testing is a valuable tool for the diagnosis of acute Q fever and should be used in outbreak situations when the onset of symptoms is <15 days earlier. Special attention is needed in the follow-up monitoring of patients with high C. burnetii DNA loads during the acute phase, as this might be an indicator for the development of a serologic profile indicative of chronic infection.     

Q Fever in Adults: Review of 66 Clinical Cases

Sixty-six cases of Q fever in adults, serologically confirmed by indirect immunofluorescence, were studied to analyze the epidemiological, clinical and therapeutic aspects of the disease. Eighty-three percent of the patients were male, and the mean age was 44.7 years. Contact with animals was recorded in 24 patients. The main clinical form of presentation was pneumonia (37 cases); eight patients had hypoxia, and five had respiratory failure. The empirical treatment consisted of macrolides in 36% of cases. Evolution was favorable in all cases. Electronic Publication     

Dysregulation of Serum Gamma Interferon Levels in Vascular Chronic Q Fever Patients Provides Insights into Disease Pathogenesis

A large community outbreak of Q fever occurred in the Netherlands in the period 2007 to 2010. Some of the infected patients developed chronic Q fever, which typically includes pathogen dissemination to predisposed cardiovascular sites, with potentially fatal consequences. To identify the immune mechanisms responsible for ineffective clearance of Coxiella burnetii in patients who developed chronic Q fever, we compared serum concentrations of 47 inflammation-associated markers among patients with acute Q fever, vascular chronic Q fever, and past resolved Q fever. Serum levels of gamma interferon were strongly increased in acute but not in vascular chronic Q fever patients, compared to past resolved Q fever patients. Interleukin-18 levels showed a comparable increase in acute as well as vascular chronic Q fever patients. Additionally, vascular chronic Q fever patients had lower serum levels of gamma interferon-inducible protein 10 (IP-10) and transforming growth factor β (TGF-β) than did acute Q fever patients. Serum responses for these and other markers indicate that type I immune responses to C. burnetii are affected in chronic Q fever patients. This may be attributed to an affected immune system in cardiovascular patients, which enables local C. burnetii replication at affected cardiovascular sites.     

Peripherally Inserted Central Venous Catheters: First Results after the Introduction in a Dutch University Medical Center

PurposeTo analyze patient outcomes and processes of insertion after the introduction of the peripherally inserted central catheter (PICC) in the University Medical Center Utrecht (UMC Utrecht) in the Netherlands.Patients and methodA prospective analysis of PICC inserted in the UMC Utrecht looking at patient characteristics, dwell time and infections.ResultsA total number of 510 PICCs in 439 patients with 17655 catheter days were analyzed using ultrasound (US) and modified Seldinger technique (MST). Overall there were 2.35 catheter-related bloodstream infections (CRBSI) per 100 devices and 0.68 infections per 1000 catheter days. When used specifically for home infusion, the CRBSI rates were 1.09 per 100 devices and 0.23 per 1000 catheter days. One advanced nurse practitioner (ANP) inserted all PICCs. Although a full sterile barrier (no hat and gown) was not used during insertion, the infection rate in our study was lower compared to the 1.1 infection per 1000 catheter days reported in a meta-analyses on CRBSI (Maki, Kluger, & Crnich, 2006).ConclusionThrough the use of modern techniques like US and MST and upper arm insertion of PICCs, the complication rate is lower compared to older techniques as shown in most prospective studies. Extended dwell time, as a positive outcome of using PICCs made more doctors decide to choose a PICC. Age of the patient did not influence dwell time or complications. Further research, preferably a randomized controlled trial, is needed to compare the subclavian catheter with the PICC as well as exploration of the effects of anticipatory choice for PICCs, specifically in immune compromised patients.     

流行性出血热患者血浆中分子物质组分分析的初步研究

流行性出血热（ＥＨＦ）与中分子物质（ＭＭＳ）有密切关系。其病死率随ＭＭＳ值的升高而增高。因此ＭＭＳ检测对ＥＨＦ预后判断具有重要价值。本文试图在宏观ＭＭＳ总量测定的基础上，检测其微观ＭＭＳ的组分，从而研究其发病机制。     

293例精神残疾15年后重新评定结果分析

目的探讨精神病残疾人重新评定的特点。方法收集了293例用国家统一的残疾标准和检查方法进行残疾等级重新评定。结果15年后重新评定本组残疾人,发现死亡率为3.22%,两次评定的诊断误诊率为0.71%,有35.48%的残疾人伴发1种以上的其他躯体性疾病,两次评定残疾等级变化差异有统计学意义(P0.01),说明残疾程度有加重趋势。结论加强残疾康复的同时,还应重视患者躯体疾病的防治,并建议精神病残疾等级评定工作,应设立初评和重新评定。     

Investigation of a Slaughterhouse-Related Outbreak of Q Fever in the French Alps

The aim of the study presented here was to describe the different epidemiological methods used to investigate an outbreak of Q fever that occurred in the spring of 1996 among inhabitants of Brian?on, a small town in the French Alps. Three approaches were used: (i) a comparison between a 2-month exhaustive serological survey among blood donors and a retrospective serological survey performed on frozen plasma collected by the transfusion centre in the spring of 1995; (ii) a serological survey performed in the general population by cluster sampling, using dried blood on blotting paper; and (iii) a case-control study. A total of 29 cases of acute Q fever were diagnosed by physicians during hospitalisations of the patients or ambulatory care. The case-control study suggested that the outbreak resulted from airborne transmission of contaminated sheep waste, which had been left uncovered in the slaughterhouse area. Such transmission may have been facilitated by the nearby heliport. The comparison between the cumulative incidence of Q fever among blood donors during the spring seasons of 1995 and 1996 confirmed the outbreak (0.38% vs. 2.58%, respectively; P<0.0001). Health authorities promptly decided to close the slaughterhouse. The use of complementary epidemiological methods allows investigators to focus on major issues related to an outbreak: timely detection of cases, identification of the source, estimations of incidence, and public health intervention. Rapid recognition and management of outbreaks in the general population of a rural region need to be improved, particularly at a time when airborne agents could be used as biological weapons. Electronic Publication     

Intellectual Functioning of Pediatric Patients with Chronic Kidney Disease: Results from the KNOW-Ped CKD

BackgroundChronic kidney disease (CKD) has a negative impact on growth and development in children and is a risk factor for neurocognitive impairment; however, there is limited research on the cognitive function of children and adolescents with CKD. This study therefore aimed to investigate the mean intelligence and risk factors for low intelligence in children and adolescents with CKD.MethodsEighty-one patients with CKD under 18 years old were included in the KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease (KNOW-Ped CKD). Participants completed either the Wechsler Intelligence Scale for Children (6–16 years), or Wechsler Adult Intelligence Scale (> 16 years).ResultsThe mean full-scale intelligence quotient (IQ) was 91 ± 19; 24.7% of participants scored a full-scale IQ below 80. Participants with a short stature (height Z scores < −1.88), failure to thrive (weight Z scores < −1.65), more severe CKD stage (≥ IIIb), longer duration of CKD (≥ 5 years), and those who were Medicare or Medicaid beneficiaries, had significantly lower mean full-scale IQs.ConclusionOn linear regression analysis, the association between the full-scale IQ, and longer duration of CKD and growth failure, remained significant after controlling for demographic and clinical variables. It is therefore necessary to investigate cognitive impairment in pediatric patients with CKD who exhibit growth failure or for a longer postmorbid period. It is believed that early interventions, such as kidney transplantation, will have a positive effect on IQ in children with CKD, as the disease negatively affects IQ due to poor glomerular filtration rate over time.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02165878","term_id":"NCT02165878"}}NCT02165878     

Hepatitis C Virus Variability: Sequence Analysis of an Isolate after 10 Years of Chronic Infection

Hepatitis C virus (HCV) variability was analyzed based upon an isolate which had caused the infection of more than 2500 women in 1978/79. Genome consensus sequences of two isolates obtained from the infectious source (HCV-AD78) and from a chronic hepatitis patient 10 years after the acute infection were determined. The entire open reading frame (ORF) exhibited 3.2 × 10^-3 nucleotide substitutions per site per year (nt). Core (0.7 × 10^-3 nt) and NS5B (1.9 × 10^-3 nt) were found to be most conserved genes, while E2 (4.7 × 10^-3 nt) with hypervariable region 1 (HVR1) (23 × 10^-3 nt) was the most variable followed by p7 (4.2 × 10^-3 nt). In the entire ORF transitions were 4.5 times more frequent than transversions while for the HVR1 this bias was turned. As an indicator of relative selective pressure on the proteins the rates of nonsynonymous to synonymous substitutions (dN/dS) were determined. The obtained values exceeded 1.0 only for E2 (dN/dS=1.3). A subdivision of the entire ORF into 88 overlapping sections, each containing 300 nucleotides, led to a more precise analysis of HCV diversity. Besides for E2 an increased variability was mainly detected for three other regions: (a) the C terminal neighbouring region of E2 including p7, (b) the genome fragment extending from approximately the middle of NS3 to NS4B, and (c) the segment corresponding to the C-terminus of the NS5A protein. The variable region in NS5A was situated carboxyterminal to the predicted interferon sensitivity determining region (ISDR). These results suggest which regions other than HVR1 might contribute to persistence of the virus by the mechanism of immunescape.     

Results from EuCliD (European Clinical Dialysis Database): impact of shifting treatment modality

BACKGROUND: The use of biocompatible high-flux membranes is more efficient than low-flux membranes in controlling a number of hemodialysis-related diseases. The aim of this cooperative study was to evaluate the 6-month effect of a switch from low- to high-flux dialysers on patients treated in 39 Spanish dialysis centres. METHODS: The clinical data used in this analysis were prospectively collected by the EuCliD database, developed to monitor the quality of treatment delivered in a large network of European Dialysis Centres. Inclusion criteria for the study were the condition of end-stage renal disease (ESRD) on chronic hemodialysis and low-flux dialysis for at least six months before the switch to high-flux dialysis. Of 1,543 patients enrolled in the study between 2000 and 2001, 1,046 patients were considered for the analysis. 497 patients were excluded because they did not complete the follow-up. Outcome measures were the reduction of pre-dialysis beta-2 microglobulin, the improvement of anemia or reduction in rHu-EPO dose required to maintain best correction of anemia, reduction of inflammatory parameters (CRP), improvement in lipid profile (Total and HDL cholesterol, tryglycerides), maintenance of nutritional status. Albumin and "dry" (post-hemodialysis) body weight were both evaluated as nutritional indexes. RESULTS: During the six months of high-flux hemodialysis, there was a significant increase in hemoglobin (from 11.55 +/- 1.41 to 11.88 +/- 1.43 g/L; p < 0.001). Considering the temporarily untreated patients on a 0 U/week dose, erythropoietin remained stable (from 5,670 +/- 4,199 to 5,657 +/- 4,411 U/week). During the second part of the follow-up, the lipid profile significantly improved (Fig. 3). Total cholesterol and triglycerides decreased significantly (p < 0.001), while HDL cholesterol increased (p = 0.006). Calculated levels of LDL cholesterol also significantly decreased (p = 0.001). Dry body weight remained stable (64.7 +/- 11.9 vs. 64.7 +/- 12.0 kg) as well as in albumin levels (3.93 +/- 0.43 vs. 3.94 +/- 0.43 g/dL) between the two modalities of treatment. The level of beta2-microglobulin significantly decreased during high-flux dialysis (33.5 +/- 14.4 vs. 26.3 +/- 8.6 mg/dL, p < 0.001). CONCLUSION: All above mentioned results may have as a common denominator an improved blood purification from uremic toxins and a reduced level of chronic sub-clinical inflammation. All together, these results seem to confirm the superiority of high-flux dialysis in terms of clinical and physiological outcomes.