Marc O. Siegel

Atrial-Esophageal Fistula after Atrial Radiofrequency Catheter Ablation

Atrial-esophageal fistula is a rare but often fatal complication of catheter radiofrequency ablation. Patients occasionally have bacteremia and have been misdiagnosed with endocarditis. Infectious diseases specialists are often consulted and need to be aware of this complication. We report a case of atrial-esophageal fistula after radiofrequency ablation that illustrates the salient features of this illness.

Is human immunodeficiency virus infection a risk factor for Strongyloides stercoralis hyperinfection and dissemination.

Strongyloides stercoralis was first identified in post-mortem examination of the gastrointestinal tract of five French soldiers from Cochin, China, in 1876. Since then it has been recognized that infection with this organism can persist for decades. This is due to an autoinfective process whereby rhabditiform larvae that are excreted by the adult worm are converted to infectious filariform larvae in the large intestine where they can then reinfect the host. Under normal conditions this conversion in humans is quite limited, with most conversions occurring in the soil. Occasionally large numbers of rhabditiform larvae transform into infective filariform larvae in the human gastrointestinal tract, which results in a more severe form of the autoinfective cycle. This is referred to as hyperinfection syndrome and can result in dissemination of the larvae to other organs in the host with potentially fatal consequences.

Clinical PathoScope: rapid alignment and filtration for accurate pathogen identification in clinical samples using unassembled sequencing data

BackgroundThe use of sequencing technologies to investigate the microbiome of a sample can positively impact patient healthcare by providing therapeutic targets for personalized disease treatment. However, these samples contain genomic sequences from various sources that complicate the identification of pathogens.ResultsHere we present Clinical PathoScope, a pipeline to rapidly and accurately remove host contamination, isolate microbial reads, and identify potential disease-causing pathogens. We have accomplished three essential tasks in the development of Clinical PathoScope. First, we developed an optimized framework for pathogen identification using a computational subtraction methodology in concordance with read trimming and ambiguous read reassignment. Second, we have demonstrated the ability of our approach to identify multiple pathogens in a single clinical sample, accurately identify pathogens at the subspecies level, and determine the nearest phylogenetic neighbor of novel or highly mutated pathogens using real clinical sequencing data. Finally, we have shown that Clinical PathoScope outperforms previously published pathogen identification methods with regard to computational speed, sensitivity, and specificity.ConclusionsClinical PathoScope is the only pathogen identification method currently available that can identify multiple pathogens from mixed samples and distinguish between very closely related species and strains in samples with very few reads per pathogen. Furthermore, Clinical PathoScope does not rely on genome assembly and thus can more rapidly complete the analysis of a clinical sample when compared with current assembly-based methods. Clinical PathoScope is freely available at: http://sourceforge.net/projects/pathoscope/.

Single-Molecule Long-Read 16S Sequencing To Characterize the Lung Microbiome from Mechanically Ventilated Patients with Suspected Pneumonia

ABSTRACT In critically ill patients, the development of pneumonia results in significant morbidity and mortality and additional health care costs. The accurate and rapid identification of the microbial pathogens in patients with pulmonary infections might lead to targeted antimicrobial therapy with potentially fewer adverse effects and lower costs. Major advances in next-generation sequencing (NGS) allow culture-independent identification of pathogens. The present study used NGS of essentially full-length PCR-amplified 16S ribosomal DNA from the bronchial aspirates of intubated patients with suspected pneumonia. The results from 61 patients demonstrated that sufficient DNA was obtained from 72% of samples, 44% of which (27 samples) yielded PCR amplimers suitable for NGS. Out of the 27 sequenced samples, only 20 had bacterial culture growth, while the microbiological and NGS identification of bacteria coincided in 17 (85%) of these samples. Despite the lack of bacterial growth in 7 samples that yielded amplimers and were sequenced, the NGS identified a number of bacterial species in these samples. Overall, a significant diversity of bacterial species was identified from the same genus as the predominant cultured pathogens. The numbers of NGS-identifiable bacterial genera were consistently higher than identified by standard microbiological methods. As technical advances reduce the processing and sequencing times, NGS-based methods will ultimately be able to provide clinicians with rapid, precise, culture-independent identification of bacterial, fungal, and viral pathogens and their antimicrobial sensitivity profiles.

Metataxonomic and Metagenomic Approaches vs. Culture-Based Techniques for Clinical Pathology.

Diagnoses that are both timely and accurate are critically important for patients with life-threatening or drug resistant infections. Technological improvements in High-Throughput Sequencing (HTS) have led to its use in pathogen detection and its application in clinical diagnoses of infectious diseases. The present study compares two HTS methods, 16S rRNA marker gene sequencing (metataxonomics) and whole metagenomic shotgun sequencing (metagenomics), in their respective abilities to match the same diagnosis as traditional culture methods (culture inference) for patients with ventilator associated pneumonia (VAP). The metagenomic analysis was able to produce the same diagnosis as culture methods at the species-level for five of the six samples, while the metataxonomic analysis was only able to produce results with the same species-level identification as culture for two of the six samples. These results indicate that metagenomic analyses have the accuracy needed for a clinical diagnostic tool, but full integration in diagnostic protocols is contingent on technological improvements to decrease turnaround time and lower costs.

HIV infection induces structural and functional changes in high density lipoproteins

BACKGROUND AND AIMS Coronary artery disease is a growing clinical problem in HIV-infected subjects. The increased risk of coronary events in this population has been linked to low levels of HDL, but the effects of HIV infection and anti-retroviral treatment (ART) on HDL structure and function remain unknown. Here, we aimed to determine the composition and function of HDL particles isolated from ART-naive and ART-positive HIV-infected patients. METHODS AND RESULTS Proteomic profiling revealed decreased levels of paraoxonase (PON) 1 and PON 3 in HDL from HIV patients relative to HDL from uninfected controls (p < 0.0001), and PON activity of HDL from control group (0.13 ± 0.01 U/μl) was significantly higher than PON activity of HDL from HIV-infected untreated subjects (0.12 ± 0.01 U/μl, p = 0.0035), subjects treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy (0.11 ± 0.01 U/μl, p < 0.0001), subjects treated with protease inhibitor (PI)-based therapy with detectable viral load (0.11 ± 0.01 U/μl, p < 0.0001), and PI-treated patients with undetectable viral load (0.12 ± 0.01 U/μl, p = 0.0164). Lipidomic profiling uncovered a negative correlation between CD4 T cell counts and particle sphingomyelin, lyso-phosphatidylcholine and ether-linked phosphatidylserine content in the ART-naive (R(2) = 0.2611, p < 0.05; R(2) = 0.2722, p < 0.05; and R(2) = 0.3977, p < 0.05, respectively) but not treated HIV-infected subjects. Functional analysis demonstrated a negative correlation between cholesterol efflux capacity of HDL and viral load in the ART-naive HIV-infected group (R(2) = 0.26, p = 0.026). CONCLUSIONS Taken together, these results indicate that HIV infection associates with a number of both protein and lipid compositional changes in HDL particles. Moreover, HIV infection affects cholesterol efflux function of HDL, thus contributing to an increased risk of atherosclerosis in this patient population.

Legionella feeleii Serotype 2 Pneumonia in a Man with Chronic Lymphocytic Leukemia: a Challenging Diagnosis

ABSTRACT Legionella feeleii has rarely been reported as causing pneumonia in patients with hematologic malignancies. We present a case of Legionella feeleii serotype 2 pneumonia with empyema in a man with chronic lymphocytic leukemia and describe the methods of identifying this organism using both standard methods and newer diagnostic techniques.

Immune reconstitution inflammatory syndrome, human herpesvirus 8 viremia, and HIV-associated multicentric Castleman disease.

Kaposis sarcoma and multicentric Castleman Disease are HIV-related disease processes that are associated with human herpesvirus 8 (HHV-8) infection. The development of multicentric Castleman disease can often be a manifestation of the immune reconstitution inflammatory syndrome phenomenon and is associated with markedly elevated levels of HHV-8 viremia, as illustrated by this case.

Sexually Transmitted Infections Among HIV-Infected Individuals in the District of Columbia and Estimated HIV Transmission Risk: Data From the DC Cohort

Abstract Background Washington, DC, has one of the highest rates of HIV infection in the United States. Sexual intercourse is the leading mode of HIV transmission, and sexually transmitted infections (STIs) are a risk factor for HIV acquisition and transmission. Methods We evaluated the incidence and demographic factors associated with chlamydia, gonorrhea, and syphilis among HIV-infected persons enrolled at 13 DC Cohort sites from 2011 to 2015. Using Poisson regression, we assessed covariates of risk for incident STIs. We also examined HIV viral loads (VLs) at the time of STI diagnosis as a proxy for HIV transmission risk. Results Six point seven percent (451/6672) developed an incident STI during a median follow-up of 32.5 months (4% chlamydia, 3% gonorrhea, 2% syphilis); 30% of participants had 2 or more STI episodes. The incidence rate of any STIs was 3.8 cases per 100 person-years (95% confidence interval [CI], 3.5–4.1); age 18–34 years, 10.8 (95% CI, 9.7–12.0); transgender women, 9.9 (95% CI, 6.9–14.0); Hispanics, 9.2 (95% CI, 7.2–11.8); and men who have sex with men (MSM), 7.7 (95% CI, 7.1–8.4). Multivariate Poisson regression showed younger age, Hispanic ethnicity, MSM risk, and higher nadir CD4 counts to be strongly associated with STIs. Among those with an STI, 41.8% had a detectable VL within 1 month of STI diagnosis, and 14.6% had a VL ≥1500 copies/mL. Conclusions STIs are highly prevalent among HIV-infected persons receiving care in DC. HIV transmission risk is considerable at the time of STI diagnosis. Interventions toward risk reduction, antiretroviral therapy adherence, and HIV virologic suppression are critical at the time of STI evaluation.

Mycobacterium Avium Complex Immune Reconstitution Inflammatory Syndrome Associated With Infliximab Use

AbstractTumor necrosis factor-α inhibitors are a mainstay therapy for patients with moderate to severe Crohn disease. Use of these agents is widely recognized to be associated with an increased risk for tuberculosis as well as fungal and intracellular bacterial infections. However, nontuberculous my