Lack of Clinical Utility of Labeled White Blood Cell Scintigraphy in Patients with Fever of Unknown Origin

Background Labeled white blood cell scintigraphy (WBCS) has been used for over 40 years to localize an infection source in patients with fever of unknown origin (FUO). It continues to be in widespread use for such patients in modern times, despite the tremendous advances in modern radiological imaging and laboratory medicine. Methods We critically evaluated the clinical contribution of WBCS performed in 132 patients with FUO at 7 hospitals from mid-2015 to the end of 2019. For each patient, all radiographic and laboratory results, and all electronic clinical notes, were carefully evaluated as many days prior to and following the scan as necessary to arrive at a final diagnosis. Results Although 50 WBCS (38%) showed positive findings, the majority of these were false positive (FP). Of the 19 true positive (TP) scans, most were already known or about to become known by tests already ordered at the time of the scan. Only 2 TP scans (1.5%) contributed to the final diagnosis, and these did so only indirectly. FP scans led to 7 unnecessary procedures. Conclusions In FUO patients for whom an infection source is not discovered following an appropriate radiographic and laboratory workup, WBCS is not a useful procedure.

Investigating methods for using genetic data to estimate the association between host factors and being an infection source with application to probing the association between HIV infection and tuberculosis transmission

Identifying host factors that influence infectious disease transmission is an important step toward developing interventions to reduce disease incidence. Recent advances in methods for reconstructing infectious disease transmission events using pathogen genomic and epidemiological data open the door for investigation of host factors that affect onward transmission. While most transmission reconstruction methods are designed to work with densely sampled outbreaks, these methods are making their way into surveillance studies, where the fraction of sampled cases with sequenced pathogens could be relatively low. Surveillance studies that use transmission event reconstruction then use the reconstructed events as response variables (i.e., infection source status of each sampled case) and use host characteristics as predictors (e.g., presence of HIV infection) in regression models. We use simulations to study estimation of the effect of a host factor on probability of being an infection source via this multi-step inferential procedure. Using TransPhylo - a widely-used method for Bayesian estimation of infectious disease transmission events - and logistic regression, we find that low sensitivity of identifying infection sources leads to dilution of the signal, biasing logistic regression coefficients toward zero. We show that increasing the proportion of sampled cases improves sensitivity and estimation of logistic regression coefficients. Application of these approaches to real world data from a population-based TB study in Botswana fails to detect an association between HIV infection and probability of being a TB infection source. We conclude that application of a pipeline, where one first uses TransPhylo and sparsely sampled surveillance data to infer transmission events and then estimates effects of host characteristics on probabilities of these events, should be accompanied by a realistic simulation study to better understand biases stemming from imprecise transmission event inference.

Prevalence of Antifungal Resistance, Genetic Basis of Acquired Azole and Echinocandin Resistance, and Genotyping of Candida krusei recovered from an International Collection

This study was designed to evaluate the prevalence of antifungal resistance, genetic mechanisms associated with in vitro induction of azole and echinocandin resistance and genotyping of Candida krusei , which is intrinsically resistant to fluconazole and is recovered from clinical and non-clinical sources from different countries. Our results indicated that all the isolates were susceptible or had the wild phenotype (WT) to azoles, amphotericin B, and only 1.27% showed non-WT for flucytosine. Although 70.88% of the isolates were resistant to caspofungin, none of them were categorized as echinocandin-resistant as all were susceptible to micafungin and no FKS1 hotspot 1 (HS1) or HS2 mutations were detected. In vitro induction of azole and echinocandin resistance confirmed the rapid development of resistance at low concentrations of fluconazole (4 μg/ml), voriconazole (0.06 μg/ml) and micafungin (0.03 μg/ml), with no difference between clinical and non-clinical isolates in the resistance development. Overexpression of ABC1 gene and FKS1 HS1 mutations were the major mechanisms responsible for azole and echinocandin resistance, respectively. Genotyping of our 79 isolates coupled with 217 other isolates from different sources and geography confirmed that the isolates belong to two main subpopulations, with isolates from human clinical material and Asia being more predominant in cluster 1, and environmental and animals isolates and those from Europe in cluster 2. Our results are of critical concern, since realizing that the C. krusei resistance mechanisms and their genotyping are crucial for guiding specific therapy and for exploring the potential infection source.

Blastomicose Sul-americana

The author, beyond the observation of 11 cases reported in this work, have realized a retrospection in the concerning literature. They tryed to uniforming sparse observations and relates, including in this work occurence, infection source, morel culture laboratorail technics, histologic, radiologic and clinical aspects, and treatment for the infirmity.

Origin of Pathogens of Grapevine Crown Gall Disease in Hokkaido in Japan as Characterized by Molecular Epidemiology of Allorhizobium vitis Strains

Crown gall is a globally distributed and economically important disease of grapevine and other important crop plants. The causal agent of grapevine crown gall is tumorigenic Allorhizobium vitis (Ti) strains that harbor a tumor-inducing plasmid (pTi). The epidemic of grapevine crown gall has not been widely elucidated. In this study, we investigated the genetic diversity of 89 strains of Ti and nonpathogenic A. vitis to clarify their molecular epidemiology. Multi-locus sequence analysis (MLSA) of the partial nucleotide sequences of pyrG, recA, and rpoD was performed for molecular typing of A. vitis strains isolated from grapevines with crown gall symptoms grown in 30 different vineyards, five different countries, mainly in Japan, and seven genomic groups A to F were obtained. The results of MLSA and logistic regression indicated that the population of genetic group A was significantly related to a range of prefectures and that the epidemic of group A strains originated mainly in Hokkaido in Japan through soil infection. Moreover, group E strains could have been transported by infected nursery stocks. In conclusion, this study indicates that both soil infection and transporting of infected nursery stocks are working as infection source in Hokkaido.

Relationship between tooth extraction and development of medication-related osteonecrosis of the jaw in cancer patients

Tooth extraction has been avoided since it has been considered a major risk factor for medication-related osteonecrosis of the jaw (MRONJ). However, MRONJ may also develop from tooth that is an infection source. This study aimed to clarify whether tooth extraction is a risk factor for the development of MRONJ in cancer patients receiving bone-modifying agents (BMAs). This retrospective observational study included 189 patients (361 jaws) from two hospitals. The risk factors of MRONJ were identified by comparing patient characteristics between those who did and did not develop MRONJ. Furthermore, the effect of tooth extraction during BMA therapy was analyzed after adjusting for confounding factors using the propensity score matching method. MRONJ occurred in 33 patients jaws. A longer duration of BMA administration, fewer number of teeth, presence of symptoms of local infection, and infected teeth were independent risk factors of MRONJ. However, tooth extraction during BMA therapy did not increase the risk. Propensity score matching analysis showed that tooth extraction significantly lowered the risk of MRONJ development. Teeth that can be an infection source increases the risk of MRONJ, and thus, they need to be extracted even during BMA administration.

Canine Circovirus in Foxes from Northern Italy: Where Did It All Begin?

Canine circovirus (CanineCV) is a recently identified virus affecting both domestic and wild carnivores, including foxes, sometimes in presence of severe clinical signs. Its circulation in wild animals can thus represent a potential threat for endangered species conservation and an infection source for dogs. Nevertheless, no data were available on its circulation in the Alps region of Northern Italy. In the present study, samples collected from 186 foxes in the period 2009–2020 from Valle d’Aosta and Veneto regions were tested using a real-time PCR assay, demonstrating a viral circulation of approximatively 2–5%, depending on the considered regions. Two complete or almost complete genome sequences were obtained, highlighting that the detected strains were part of a so defined “fox only” clade, which suggests that, despite common contact opportunities, Alps foxes are not involved in frequent transmission events to domestic dogs. Such genetic isolation could be at least partially attributed to some sort of independent evolution occurred in the foxes, leading to species barrier. Additionally, CanineCV strains in foxes from Italy were unexpectedly related to those previously identified in foxes from the United Kingdom and Scandinavian area. Combining the history of fox distribution in Europe since the last glacial maximum (LGM) with the viral history allowed us to speculate a long-standing coexistence between European canine circovirus and this host, justifying the peculiar geographic distribution and evolutionary paths of the fox infecting clade.

Challenges in Hospital-Acquired COVID-19 Surveillance and Attribution of Infection Source

We performed surveillance for hospital-acquired COVID-19 (HA-COVID-19) and compared time-based, electronic definitions to real-time adjudication of the most likely source of acquisition. Without real-time adjudication, nearly 50% of HA-COVID-19 cases identified using electronic definitions were misclassified. Both electronic and traditional contact tracing methods likely underestimated the incidence of HA-COVID-19.

A qPCR Assay for the Fast Detection and Quantification of Colletotrichum lupini

White lupin (Lupinus albus) represents an important legume crop in Europe and other parts of the world due to its high protein content and potential for low-input agriculture. However, most cultivars are susceptible to anthracnose caused by Colletotrichum lupini, a seed- and air-borne fungal pathogen that causes severe yield losses. The aim of this work was to develop a C. lupini-specific quantitative real-time TaqMan PCR assay that allows for quick and reliable detection and quantification of the pathogen in infected seed and plant material. Quantification of C. lupini DNA in dry seeds allowed us to distinguish infected and certified (non-infected) seed batches with DNA loads corresponding to the disease score index and yield of the mother plants. Additionally, C. lupini DNA could be detected in infected lupin shoots and close to the infection site, thereby allowing us to study the disease cycle of this hemibiotrophic pathogen. This qPCR assay provides a useful diagnostic tool to determine anthracnose infection levels of white lupin seeds and will facilitate the use of seed health assessments as a strategy to reduce the primary infection source and spread of this disease.

The epidemic of Q fever in 2018 to 2019 in Zhuhai city of China determined by metagenomic next-generation sequencing

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018–2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.