Use Of Routine Surveillance Research Articles

Population Structure of Listeria monocytogenes in Emilia-Romagna (Italy) and Implications on Whole Genome Sequencing Surveillance of Listeriosis.

The population structure of human isolates of Listeria monocytogenes in Emilia-Romagna, Italy, from 2012 to 2018 was investigated with the aim of evaluating the presence of genomic clusters indicative of possible outbreaks, the proportion of cluster-associated vs. sporadic isolates and different methods and metrics of genomic analysis for use in routine surveillance. In the 2012–2018 period the notification rate of confirmed invasive cases in Emilia-Romagna was 0.91 per 100,000 population per year, more than twice the average rate of EU countries. Out of the total 283 cases, 268 (about 95%) isolates were typed through whole genome sequencing (WGS) for cluster detection with methods based on core-genome multi-locus sequence typing and single nucleotide polymorphisms. Between 66 and 72% of listeriosis cases belonged to genomic clusters which included up to 27 cases and lasted up to 5 years. This proportion of cluster-associated cases is higher than previously estimated in other European studies. Rarefaction analysis, performed by reducing both the number of consecutive years of surveillance considered and the proportion of isolates included in the analysis, suggested that the observed high proportion of cluster-associated cases can be ascribed to the long surveillance duration (7 years) and the high notification and typing rates of this study. Our findings show that a long temporal perspective and high surveillance intensity, intended as both exhaustiveness of the system to report cases and high WGS-typing rate, are critical for sensitive detection of possible outbreaks within a WGS-based surveillance of listeriosis. Furthermore, the power and complexity of WGS interpretation emerged from the integration of genomic and epidemiological information in the investigation of few past outbreaks within the study, indicating that the use of multiple approaches, including the analysis of the accessory genome, is needed to accurately elucidate the population dynamics of Listeria monocytogenes.

Identification of maize lethal necrosis disease causal viruses in maize and suspected alternative hosts through small RNA profiling

AbstractMaize lethal necrosis disease (MLND) is a devastating viral disease of maize caused by double infection with Maize chlorotic mottle virus (MCMV) and any one of the Potyviridae family members. Management of MLND requires effective resistance screening and surveillance tools. In this study, we report the use of small RNA (sRNA) profiling to detect MLND causal viruses and further the development of alternative detection markers for use in routine surveillance of the disease‐causing viruses. Small RNAs (sRNAs) originating from five viruses namely MCMV, Sugarcane mosaic virus (SCMV), Maize streak virus (MSV), Maize‐associated totivirus (MATV) and Maize yellow mosaic virus (MYMV) were assembled from infected maize samples collected from MLND hot spots in Kenya. The expression of the identified viral domains was further validated using quantitative real‐time PCR. New markers for the detection of some of the MLND causal viruses were also developed from the highly expressed domains and used to detect the MLND‐causative viruses in maize and alternative hosts. These findings further demonstrate the potential of using sRNAs especially from highly expressed viral motifs in the detection of MLND causal viruses. We report the validation of new sets of primers for use in detection of the most common MLND causal viruses MCMV and SCMV in East Africa.

Routine Blood Investigations Have Limited Utility in Routine Surveillance of High-Grade Lymphomas (HGL) in Remission after First-Line Therapy

BackgroundPatients with HGL achieving complete remission (CR) after first-line combination chemotherapy undergo regular surveillance to detect early signs of relapse. As follow-up imaging is associated with increased radiation-related risk and minimal benefit in asymptomatic (aSx) patients, imaging as surveillance is no longer routine. (Eichenauer Ann Oncol 2014, Tilly Ann Oncol 2015) Regular laboratory testing (Labs) still feature in internationally-recognised surveillance guidelines (eg NCCN), despite limited evidence in the modern era for their use in relapse detection. Studies conducted prior to modern imaging (PET/CT) and use of rituximab suggested LDH and ESR may be useful, and more recently the absolute lymphocyte count (ALC) and lymphocyte-monocyte ratio (LMR) have shown promise in small series (Weeks JCO 1991, Henry-Amar Ann Int Med 1991,Wei Leuk Lymph 2015, Porrata Leukemia 2010). However large scale data are lacking hence there is no consensus on the value and optimum frequency of specific laboratory parameters for use in routine surveillance of HGL.MethodsWe conducted a retrospective analysis of patients with histologically-proven cHL, DLBCL, T-cell lymphoma or Burkitt lymphoma receiving curative-intent treatment over a 15-year period. Eligible patients were aged≥16years, in CR for ≥3 months & had >12months follow-up. Primary CNS lymphoma, HIV-associated lymphomas and transformation from indolent subtypes were excluded. Data were collated from patient records. Laboratory results were considered abnormal if a) FBE, ALC, neutrophil count, absolute monocyte count (AMC), ESR or LDH fell outside local laboratory normal limits b) the derangement was not present previously and c) could not be explained by a concurrent medical condition. Abnormal Lab results were investigated at clinician discretion. Labs were evaluated based on their independent ability to detect relapse within 3 months of confirmation. Kaplan-Meier method was used for survival analysis and compared by the log-rank test between groups.ResultsBetween 2000-2015, 346 eligible patients underwent 3048 outpatient visits. Median follow-up was 30 months (range 3-184). Labs were performed at 90% of appointments: FBE in 99.7%, LDH in 78% (of NHL), ESR in 38% (of HL) with abnormalities in 26%, 12% and 16% respectively. Fifty-five patients relapsed (16%). Routine Labs detected aSx relapse in 3/55 (5%); routine imaging detected 9/55 relapses (16%) and clinical symptoms/signs lead to diagnosis of relapse in 43/55 (78%; 19/43 were unscheduled visits). Unscheduled appointments due to patient-reported symptoms (3% of all visits) showed a significantly stronger association with relapse than scheduled visits (OR 50.4, p<0.001).Table 1 presents sensitivity, specificity, PPV and NPV of Labs, demonstrating in particular a low PPV and high NPV. ALC, AMC and LMR were very poor markers for relapse, with area under the curve of 0.517, 0.529 and 0.576 respectively. In addition, an abnormal Lab result prompted a change in management for only 16% of aSx patients, (37 imaging, 38 repeat Labs, 22 earlier scheduling of next review), compared to 59% with symptoms/signs. In 43 episodes, abnormal Labs lead to further investigations which were subsequently negative (25 imaging, 6 biopsies, 11 repeat Labs).There was no significant difference in OS between patients who had Labs performed ≥3 months prior to documented relapse versus patients who did not (p=0.88, figure 1).ConclusionAlthough normal Lab results have a high NPV for relapse, most HGL relapses are detected by patient-reported symptoms, often at unscheduled visits. Abnormal Labs in aSx patients infrequently trigger a change in management. Routine Labs rarely detect relapse in aSx patients with HGL in CR after primary curative-intent chemotherapy, demonstrate unacceptably poor performance characteristics, have no impact on survival and have limited value in routine surveillance. [Display omitted] [Display omitted] DisclosuresHawkes:BMS: Other: travel expenses, Research Funding; Takeda: Other: travel expenses; Merck Serono: Research Funding.

Guideline Familiarity Predicts Variation in Self-Reported Use of Routine Surveillance PET/CT by Physicians Who Treat Head and Neck Cancer

Use of routine surveillance testing beyond guideline recommended levels is common in many oncologic disciplines, including head and neck cancer. The impact of guideline familiarity and other physician characteristics on surveillance imaging use are not well understood. A cross-sectional national survey was performed of physicians responsible for surveillance of patients with head and neck squamous cell carcinoma (HNSCC). The primary outcome was self-reported use of routine surveillance PET/CT in asymptomatic patients. A secondary outcome was familiarity with guideline recommendations. Using multivariable regression, the impact of guideline familiarity and other physician characteristics on PET/CT use was examined. Of the 502 responders, 79% endorsed ever using PET/CT scans for routine surveillance imaging, and 39% were high imaging users (used PET/CT scans on more than half of their asymptomatic patients); 76% were familiar with the NCCN Clinical Practice Guidelines in Oncology for Head and Neck Cancers recommending against routine surveillance PET/CT scans. Although guideline familiarity was associated with being a low imaging user or a never-user, among those who were familiar with guidelines, 31% were nonetheless high imaging users and 73% endorsed ever using PET/CT scans. In multivariable analysis controlling for physician characteristics, guideline familiarity was the strongest predictor of PET/CT use. Familiarity with the NCCN Guidelines predicts self-reported routine surveillance PET/CT use among physicians who treat patients with HNSCC. However, given the observed variation and high levels of imaging even among physicians who are familiar with the guidelines, further research should examine the reasons physicians choose to use surveillance PET/CT scans.

Use of an Electronic Surveillance System to Reduce Incidence of Klebsiella Pneumoniae in a Neonatal Intensive Care Unit

Pneumonia is a severe complication in extremely preterm infants in the Neonatal Intensive Care Unit (NICU). It is associated with both an increased length of stay and a high mortality rate. In our 83-bed NICU, the use of routine surveillance and review of lab data does not provide a consistent approach to identifying trends. Through the use of an electronic surveillance system, monthly pattern reports are used to promptly identify and control infections.

A new pattern-based method for identifying recent HIV-1 infections from the viral env sequence

The long asymptomatic stage of HIV infection poses a great challenge in identifying recent HIV infections. This is a bottleneck for monitoring HIV epidemic trends and evaluating the effectiveness of national AIDS control programs. Several serological methods were used to address this issue with some success. Because of high false-positive rates in patients with advanced infection or in ART treatment, UNAIDS still hesitates to recommend their use in routine surveillance. We developed a new pattern-based method for measuring intra-patient viral genetic diversity for determination of recent infections and estimation of population incidence. This method is verified by using several datasets (424 subtype B and 77 CRF07_BC samples) with clearly identified HIV-1 infection times. Pattern-based diversities of recent infections are significantly lower than that of chronic ones. With larger window periods varying from 200 to 350 days, a higher accuracy (90%-95%) not affected by advanced disease nor ART treatment could be obtained. The pattern-based genetic method is supplementary to the existing serology-based assays, both of which could be suitable for use in low and high epidemic regions, respectively.

Clonal Complexes of Campylobacter jejuni Identified by Multilocus Sequence Typing Are Reliably Predicted by Restriction Fragment Length Polymorphism Analyses of the flaA Gene

Multilocus sequence typing (MLST) has provided important new insights into the population structure of Campylobacter jejuni and is rapidly becoming the gold standard for typing this species. However, the methodology is comparatively costly and slow to perform for the routine surveillance testing of large numbers of isolates required by public health laboratories. Restriction fragment length polymorphism analysis of the flaA gene (RFLP-flaA) and sequencing of the variable region in the fla locus (SVR-fla) were compared to MLST to determine if a low cost alternative could be found that reliably predicts clonal lineage (as determined by MLST). An isolate of C. jejuni from each of 153 patients from New South Wales, Australia, collected sequentially over a period of 30 months from 1999 to 2001 and comprising 40 sequence types (ST) from 15 clonal complexes (CC) was examined. Of 15 CC, 12 were represented by more than one isolate and a predominant RFLP-flaA type was found for 10 (83%). Of these, seven (70%) correctly predicted the predominant MLST CC with a probability of >0.8. Of 40 STs detected, 19 were reported for the first time, 9 of which were represented by more than one isolate. Eight of these were represented by a single RFLP-flaA type. Only two of eight major SVR-fla types were able to predict CC with a probability of >0.8, indicating that flaA-RFLP is a more reliable predictor of CC than SVR-fla and thus offers an alternative to MLST for use in routine surveillance.

Pelvic relapses of uterine neoplasms: transvaginal sonographic and Doppler features

Objective. To describe the sonographic and power Doppler features of pelvic relapses in endometrial and cervical cancer. Methods. We retrospectively analyzed the preoperative transvaginal sonographic reports of 45 women with a histological diagnosis of pelvic relapse. The three diameters of the lesion were recorded; then the shape, margins, content (solid or cystic), and location were analyzed. A subjective assessment of the vascularization (vascular score) was obtained with power Doppler. Results. Twenty-six patients had pelvic recurrence from endometrial cancer and 19 from cervical cancer. In 36 (80%) patients, the recurrence was a central pelvic mass located on the vaginal apex, while in six cases (13%), it was diagnosed as a pelvic side-wall recurrence, and in three (7%), the recurrence occupied the whole pelvis. The recurrences had diameters ranging from 1.0 to 6.8 cm (mean diameter: 3.0 cm, standard deviation: 1.5). In 44/45 cases (98%), the recurrence appeared as a solid nodular mass, while in one case (2%), it was defined as a cystic mass. In 32 (71%) women, the mass showed a hypoechoic content with respect to the surrounding bowel, while in 13 (29%), it manifested a nonhomogeneous content. Vascularization of the mass was assessed in all patients before surgery; in all cases, it was possible to visualize randomly dispersed blood vessels in the context of the relapse. The vascular score revealed scarce blood vessels in 19 relapses, moderate flow in 23, and abundant flow in three cases. Conclusions. Knowledge of the spectrum of ultrasonographic findings of pelvic relapses will help the physician in diagnosing a recurrent malignant disease at an early stage, when cure rates are high. The widespread availability and low cost of transvaginal sonography (TVS) support its use in routine surveillance of patients operated for uterine neoplasms.

The Role of Surveillance CT Scans in Patients with Diffuse Large B-cell Non-Hodgkin's Lymphoma

The use of routine surveillance computed tomography (CT) scans in the follow-up of patients with diffuse large B-cell lymphoma may allow the detection of early asymptomatic relapse. On this basis, CT scans are frequently included in follow-up schedules, but the utility of this investigation in this setting has never been determined. This study evaluated the effectiveness of routine surveillance CT scans performed 3 and 12 months after completion of chemotherapy in patients with diffuse large B-cell lymphoma who had achieved a complete response. One hundred and seventeen patients with diffuse large B-cell lymphoma achieved complete remission at the Royal Marsden Hospital using first line combination chemotherapy between January 1992 and January 2000. The median follow-up was 4.6 years and 35 patients subsequently relapsed. Relapse was associated with the development of new symptoms and/or signs in 86% of cases. Only 5.7% of relapses were detected in asymptomatic patients using surveillance CT scans. Routine surveillance CT scans are of limited value in detecting asymptomatic early relapse and other approaches are required in order to identify patients destined to relapse at an earlier stage.