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Objectives: We sought to assess the performance of 3 laboratory tests on blood specimens for direct detection of Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA), in patients tested at a single medical institution in New York State., Methods: Direct tests included microscopic blood smear examination for intragranulocytic inclusions, polymerase chain reaction (PCR), and culture using the HL-60 cell line. The HGA cases testing positive by only 1 direct test were not included, unless HGA was confirmed by acute or convalescent serology using an indirect immunofluorescent assay., Results: From 1997 to 2009, 71 patients with HGA were diagnosed by at least 1 of the 3 direct test methods. For the subgroup of 55 patients who were tested using all 3 methods, culture was positive for 90.9% (50/55) vs 81.8% (45/55) for PCR vs 63.6% (35/55) for blood smear (P =.002). Most cultures (79.3%) were detected as positive within 1 week of incubation., Conclusions: Although using culture to detect A phagocytophilum is likely not amenable for implementation in most hospital laboratories, in our experience, culture had the highest yield among the direct tests evaluated., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Coronavirus disease 2019 (COVID-19) reverse-transcription polymerase chain reaction employee testing was implemented across New York University Langone Health. Over 8 weeks, 14 764 employees were tested; 33% of symptomatic employees, 8% of asymptomatic employees reporting COVID-19 exposure, and 3% of employees returning to work were positive. Positivity rates declined over time, possibly reflecting the importance of community transmission and efficacy of personal protective equipment., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We describe the rapid and ongoing emergence across multiple US cities of a new multidrug-resistant Escherichia coli clone-sequence type (ST) 1193-resistant to fluoroquinolones (100%), trimethoprim-sulfamethoxazole (55%), and tetracycline (53%). ST1193 is associated with younger adults (age <40 years) and currently comprises a quarter of fluoroquinolone-resistant clinical E. coli urine isolates.

Two hallmarks of advanced atherosclerosis are calcification and fibrosis. We hypothesized that Chlamydia pneumoniae infection may contribute to atherosclerosis by inducing the conversion of vascular smooth muscle cells to calcifying cells or by converting mesenchymal stem cells to osteochondrocytic or fibroblastic phenotypes. In this study, direct infection of bovine aortic smooth muscle cells (BSMCs) did not induce the expression of alkaline phosphatase or the deposition of extracellular calcium phosphate. However, conditioned media from C. pneumoniae-infected macrophages accelerated conversion of BSMCs to a calcifying phenotype. Treatment of the conditioned media with an anti-TNF-alpha blocking antibody abrogated this stimulatory effect. Treatment of perivascular Sca-1+, CD31-, CD45- cells from apoE-/- mouse aortas with the conditioned media from infected macrophages induced the Sca-1+ cells to produce collagen II, an additional marker of an osteochondrocytic phenotype. Treatment of mouse coronary perivascular Sca-1+, CD31-, CD45- cells with the supernatant from homogenates of C. pneumoniae-infected mouse lungs as compared to noninfected lungs induced expression of the Collagen 1α1 gene and deposition of collagen. Therefore, an increase in plasma cytokines or other factors in response to respiratory infection with C. pneumoniae or infection of macrophages within the blood vessel could contribute to both calcification and fibrosis of advanced atherosclerotic lesions., (© 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.)

Several lines of evidence have associated Chlamydia pneumoniae with cardiovascular disease including acceleration of atherosclerotic lesion progression in hyperlipidemic animal models by infection. Many of the pro-atherogenic effects of oxidized low-density lipoprotein (ox-LDL) occur through the activation of the lectin-like ox-LDL receptor-1 (LOX-1). Chlamydia pneumoniae upregulates the expression of the LOX-1 mRNA, promotes the uptake of ox-LDL, and utilizes the LOX-1 receptor for infectivity. The overall goal of this study was to determine whether C. pneumoniae organisms upregulated LOX-1 protein expression in vascular cells and whether upregulation of pro-atherogenic factors by C. pneumoniae occurred through LOX-1. Chlamydia pneumoniae induced LOX-1 protein expression in both endothelial cells and RAW macrophages. Upregulation was prevented by preincubation of cells with LOX-1 antibody prior to infection. Similarly, C. pneumoniae upregulated protein expression of adhesion molecules, MMP-1, and MMP-3, which was mitigated by anti-LOX-1 antibody. Prior treatment of organisms with PNGase, which removes the chlamydial glycan that is N-linked to the major outer membrane, abolished C. pneumoniae upregulation of LOX-1. These studies suggest that activation of LOX-1 expression occurs through binding of the chlamydial glycan and provides one mechanism by which C. pneumoniae infection could play a role in the pathogenesis of atherosclerosis., Competing Interests: The authors have no conflicts of interest to declare., (© 2013 Federation of European Microbiological Societies.)

Background: Lyme disease is transmitted by the bite of the Ixodes scapularis tick, which can also transmit Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA). Conflicting data exist on the frequency of coinfection and on whether Lyme-HGA coinfected patients have more symptoms than patients with Lyme disease alone., Methods: Blood culture and serology were used to detect HGA infection in patients with early Lyme disease who presented with erythema migrans. The rate of coinfection was determined using different definitions. The clinical and laboratory features of Lyme-HGA coinfection were compared with that of the individual infections., Results: Among 311 patients with erythema migrans, the frequency of coinfection with HGA varied from 2.3% to 10.0%, depending on the definition used (P < .001). Only 1 of 4 groups with presumed coinfection had significantly more symptoms than patients with Lyme disease alone P < .05. High fever and cytopenia were less common in Lyme-HGA coinfection than in patients with HGA alone., Conclusion: The results of this study indicate that how HGA is defined in patients with early Lyme disease has an impact on the apparent rate of coinfection and the severity of illness. The findings also suggest that HGA may be less severe than is usually believed, suggesting the existence of referral bias in testing patients preferentially who present with high fever or cytopenia.

Background: Standard 2-tiered immunoglobulin G (IgG) testing has performed well in late Lyme disease (LD), but IgM testing early in the illness has been problematic. IgG VlsE antibody testing, by itself, improves early sensitivity, but may lower specificity. We studied whether elements of the 2 approaches could be combined to produce a second-tier IgG blot that performs well throughout the infection., Methods: Separate serum sets from LD patients and control subjects were tested independently at 2 medical centers using whole-cell enzyme immunoassays and IgM and IgG immunoblots, with recombinant VlsE added to the IgG blots. The results from both centers were combined, and a new second-tier IgG algorithm was developed., Results: With standard 2-tiered IgM and IgG testing, 31% of patients with active erythema migrans (stage 1), 63% of those with acute neuroborreliosis or carditis (stage 2), and 100% of those with arthritis or late neurologic involvement (stage 3) had positive results. Using new IgG criteria, in which only the VlsE band was scored as a second-tier test among patients with early LD (stage 1 or 2) and 5 of 11 IgG bands were required in those with stage 3 LD, 34% of patients with stage 1, 96% of those with stage 2, and 100% of those with stage 3 infection had positive responses. Both new and standard testing achieved 100% specificity., Conclusions: Compared with standard IgM and IgG testing, the new IgG algorithm (with VlsE band) eliminates the need for IgM testing; it provides comparable or better sensitivity, and it maintains high specificity.

Objectives: To evaluate whether antimicrobial chemotherapy prevents acceleration of atherosclerotic lesion development induced by infection with Chlamydia pneumoniae., Methods: ApoE-deficient mice which develop hyperlipidaemia and atherosclerosis spontaneously were inoculated intranasally with C. pneumoniae. Animals were treated with azithromycin for 6 weeks after the third inoculation and the atherosclerotic lesion areas in the aortic sinus were measured by computer-assisted morphometry., Results: At 12 weeks post-infection, infected untreated animals developed significantly larger lesion areas compared with sham-inoculated controls (8.7 x 10(4)+/-2.3 x 10(4) microm(2) versus 5.6 x 10(4)+/-2.4 x 10(4) microm(2)). However, there were no differences in lesion size of infected mice treated with azithromycin in comparison with untreated infected controls (11.0 x 10(4)+/-3.0 x 10(4) microm(2) versus 8.7 x 10(4)+/-2.3 x 10(4) microm(2))., Conclusions: Antibiotic treatment against C. pneumoniae has no beneficial effects on hyperlipidaemia-induced atherosclerosis accelerated by C. pneumoniae in a mouse model.

Recently, a number of refinements in diagnostic modalities for detection of Borrelia burgdorferi infection have been developed. These include large-volume blood cultures, quantitative polymerase chain reaction (PCR) techniques, and 2-stage serologic testing. In the present study, we compared 6 diagnostic modalities in 47 adult patients who had a clinical diagnosis of erythema migrans. Quantitative PCR on skin biopsy-derived material was the most sensitive diagnostic method (80.9%), followed by 2-stage serologic testing of convalescent-phase samples (66.0%), conventional nested PCR (63.8%), skin culture (51.1%), blood culture (44.7%), and serologic testing of acute-phase samples (40.4%). Results of all assays were negative for 3 patients (6.4%). We conclude that the clinical diagnosis of erythema migrans is highly accurate in an area where B. burgdorferi is endemic if it is made by experienced health care personnel, but some patients with this diagnosis may not have B. burgdorferi infection. No single diagnostic modality is suitable for detection of B. burgdorferi in every patient with erythema migrans.

It has been shown that infection of human endothelial cells by Chlamydia pneumoniae is enhanced by co-culturing endothelial cells with human monocytes and is mediated by monocyte-derived soluble factors. This study was conducted to identify the infectivity-enhancing factor. Serum-free conditioned medium of human monocytic cells was fractionated by ultrafiltration. The enhancing activity was found in the fraction in the molecular mass range between 5000 and 10,000 kDa. Recombinant human insulin-like growth factor (IGF)-1 or -2, with a molecular mass of 7500 kDa, was added to the culture medium of human endothelial cells for growing C. pneumoniae. Only IGF-2 enhanced C. pneumoniae growth. Pretreatment of the conditioned medium with a monoclonal antibody against IGF-2 blocked the enhancing activity. This suggests that the infectivity-enhancing factor is IGF-2 and that paracrine interactions between monocytes and endothelial cells in vivo can induce secretory products and sustain infection with C. pneumoniae within atherosclerotic lesions.

To describe the changes that occur in blood count parameters during the natural course of human granulocytic ehrlichiosis, we designed a retrospective cross-sectional case study of 144 patients with human granulocytic ehrlichiosis and matched controls who had a different acute febrile illness. Patients from New York State and the upper Midwest were evaluated from June 1990 through December 1998. Routine complete blood counts and manual differential leukocyte counts of peripheral blood were performed on blood samples that were collected during the active illness, and values were recorded until the day of treatment with an active antibiotic drug. Thrombocytopenia was observed more frequently than was leukopenia, and the risk of having ehrlichiosis varied inversely with the granulocyte count and the platelet count. Patients with ehrlichiosis displayed relative and absolute lymphopenia and had a significant increase in band neutrophil counts during the first week of illness. Knowledge of characteristic complete blood count patterns that occur during active ehrlichiosis may help clinicians to identify patients who should be evaluated specifically for ehrlichiosis and who should receive empiric antibiotic treatment with doxycycline.

Atherosclerotic lesions are initiated and progress largely as a result of a chronic, fibroproliferative, inflammatory response. This review discusses how Chlamydia pneumoniae could conceivably contribute to this chronic inflammatory response and reports on recent in vivo and in vitro studies. In vivo studies in mice demonstrate that C. pneumoniae infection is disseminated to the artery wall following infection in the lung by alveolar macrophages. Recent in vitro studies show that infected U937 cells can directly transfer infection to endothelial cells and can indirectly increase the susceptibility of endothelial cells to C. pneumoniae infection. Loading of RAW 264.7 cells with modified forms of low-density lipoprotein increases the resistance of the cells to C. pneumoniae infection and also increases the susceptibility to the combined toxic effects of modified lipids and C. pneumoniae infection.

To improve the accuracy of testing for antibody to Borrelia burgdorferi, 2-stage conditional testing has been recommended, in which sera that yield positive or equivocal results in a first-stage test (e.g., an ELISA) are then tested by immunoblot assay. The increased specificity anticipated with sequential testing, however, depends on immunoblot assays and ELISAs being independent tests. To examine whether they are independent, control serum samples were tested with 2 different commercially available IgM ELISAs and with an IgM immunoblot assay kit. The frequency of false-positive IgM immunoblot assays was significantly higher with ELISA-reactive than with ELISA-negative serum samples (P

To determine the mechanism(s) by which Chlamydia pneumoniae homes to and establishes persistent infection in atheromatous lesions, the effect of the interaction of monocytes/macrophages (U937 cells) with human umbilical vein endothelial cells (HUVECs) and transformed human arterial endothelial cells (HMEC-1s) on the susceptibility of endothelial cells to infection with C. pneumoniae was investigated. Infection was enhanced 4.7-fold (HUVECs) and 4.4-fold (HMEC-1s) after coculture at monocyte-to-endothelial cell ratios of 5 and 2.5, respectively. U937 cells also directly transmitted infection to the endothelial cells, and addition of U937 cell-conditioned media dose-dependently enhanced the infectivity 2.0- to 2.5-fold. The stimulation of infectivity was specific to endothelial cells, because coculturing of monocytes with epithelial cells did not enhance the susceptibility of epithelial cells to infection. The susceptibility of endothelial cells to infection with C. trachomatis and C. psittaci was not enhanced by the monocyte-derived factor(s).

Accumulating evidence supports an association between Chlamydia pneumoniae infection and atherosclerosis. To determine whether there is a causal relationship, the effects of chronic infection with C. pneumoniae on the development of atherosclerosis in apolipoprotein E (apoE)-deficient mice were evaluated. Eight-week-old male apoE-deficient mice were inoculated intranasally with C. pneumoniae three times, at 8, 9, and 10 weeks of age. The combined area of atherosclerotic lesions in the lesser curvature of the aortic arch was measured en face by computer-assisted morphometry. The lesion area was 2.4-fold greater (P=.05) at 16 weeks of age and 1.6-fold greater (P=.05) at 20 weeks of age in infected mice than in control mice. There were no differences in total plasma cholesterol levels between groups. This study demonstrates that C. pneumoniae infection accelerates the progression of atherosclerosis in the aortic arch of apoE-deficient mice.

We describe the clinical and laboratory manifestations of human granulocytic ehrlichiosis (HGE) in eight patients for whom cultures were positive for the HGE agent and compare them with 15 patients for whom cultures were negative but who fulfilled a modified New York State Surveillance definition for HGE. Polymerase chain reaction analysis was positive in 8 (100%) of 8 culture-positive cases vs. 3 (20%) of 15 culture-negative cases (P < .001), morulae were detected in 7 (100%) of 7 culture-positive cases in which tests were performed vs. 0 of 15 culture-negative cases (P < .001), and a fourfold change in antibody titer was demonstrated in 6 (75%) of 8 culture-positive cases vs. 9 (69%) of 13 culture-negative cases (P = not significant). Patients for whom cultures were positive had higher mean oral temperatures +/- SD at presentation than did patients for whom cultures were negative (38.6 degrees C +/- 0.7 degree C vs. 37.2 degrees C +/- 0.8 degree C, respectively; P = .002). Other symptoms and signs were not significantly different between the two groups. Multivariate analysis revealed that the lymphocyte count at presentation was significantly lower in culture-positive cases than in culture-negative cases. Clinical response to treatment was similar in the two groups. Culture confirmation of HGE is the gold standard for defining the sensitivity and specificity of other diagnostic tests presently being developed.

Each method used for the extraction and isolation of intimal lipoproteins has advantages and disadvantages. Gentle extraction methods are needed to characterize subtle modifications in the structure and biologic properties of the lipoproteins, whereas more aggressive methods are needed if the goal is to maximize the yield of lipoproteins from atherosclerotic arteries. The present paper evaluates different methods used for the isolation of intimal lipoproteins. Normal intima contains remnant-like and low density lipoprotein (LDL)-like particles that more strongly stimulate cholesterol esterification in macrophages than do control plasma LDL. Both fractions contain apolipoprotein (apo) E but neither shows clear signs of oxidative modification. LDL-like particles from atherosclerotic lesions, on the other hand, contain malondialdehyde- and 4-hydroxynonenal-lysine adducts in apo B, are chemotactic for monocytes and show increased degradation in macrophages, a process that oxidized LDL prepared in vitro can compete with. The findings support the conclusion that at least a portion of the LDL isolated from atherosclerotic lesions is similar, if not identical, to oxidatively modified LDL.