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In June 2021, a cluster of seven cases of Campylobacter fetus infections occurred in a rehabilitation center and caused significant morbidity in elderly patients including five with bacteremia and two with osteoarticularmedical device infections. The genetic identity identified by whole genome sequencing of the different Campylobacter fetus strains confirms a common source. This foodborne illness outbreak may have resulted from the consumption of unpasteurized dairy products, such as a cow's raw milk cheese resulting from a farm-to-fork strategy. [ABSTRACT FROM AUTHOR]

Depletion of CD[4.sup.+] T cells from the gut occurs rapidly during acute HIV-1 infection. This has been linked to systemic inflammation and disease progression as a result of translocation of microbial products from the gut lumen into the bloodstream. Combined antiretroviral therapy (cART) substantially restores CD[4.sup.+] T cell numbers in peripheral blood, but the gut compartment remains largely depleted of such cells for poorly understood reasons. Here, we show that a lack of recruitment of CD[4.sup.+] T cells to the gut could be involved in the incomplete mucosal immune reconstitution of cART-treated HIV-infected individuals. We investigated the trafficking of CD[4.sup.+] T cells expressing the gut-homing receptors CCR9 and integrin α4β7 and found that many of these T cells remained in the circulation rather than repopulating the mucosa of the small intestine. This is likely because expression of the CCR9 ligand CCL25 was lower in the small intestine of HIV-infected individuals. The defective gut homing of CCR[9.sup.+]β[7.sup.+] CD[4.sup.+] T cells - a population that we found included most gut-homing Th17 cells, which have a critical role in mucosal immune defense - correlated with high plasma concentrations of markers of mucosal damage, microbial translocation, and systemic T cell activation. Our results thus describe alterations in CD[4.sup.+] T cell homing to the gut that could prevent efficient mucosal immune reconstitution in HIV-infected individuals despite effective cART., Introduction The immune responses to the antigens encountered along the intestinal mucosa surfaces are mainly initiated in inductive sites of the gut-associated lymphoid tissue (GALT), Peyer's patches, and mesenteric lymph [...]

Typhoid fever caused by Salmonella enterica serotype Typhi (hereafter referred to as Salmonella Typhi) remains a major health problem in the developing world (1). Treatment with appropriate antimicrobial drugs has [...]

To the Editor: New World cutaneous leishmaniasis (CL), a zoonotic disease, is increasingly seen among travelers returning from Latin American countries, particularly from Bolivia, Belize, and French Guiana (1). The [...]

The aim of the study was to identify high-risk groups and the determinants of late HIV diagnosis in France in the era of highly active antiretroviral therapy (HAART), from January 1996 to June 2005. Informations were collected from an electronic medical record of all HIV-1-infected patients who sought care in six HIV reference centers in France, constituting a prospective multicentric cohort. Patients were defined as 'late testers' if they had presented with either symptoms of clinical AIDS or a CD4 cell count less than 200/[mm.sup.3] during the year of diagnosis, as 'nonlate' if their CD4 count was above 200, and as 'unknown' if CD4 cell count in the year at the time of diagnosis was not documented. Among the 4516 patients available for analysis, the percentage of late testing was 38% (n = 1718) and decreased after 2003 (31.5% in 2004-2005). This percentage was higher in heterosexual men (48.2%) than in homosexual men (31.7%) or heterosexual women (32.6%) and was higher for patients older than 30. Heterosexual men living in a couple with children had a higher risk of late testing (odds ratio [OR] = 1.65, 95% confidence interval [CI]: 1.03 to 2.66), while heterosexual women in a couple without children had a lower risk (OR = 0.46, 95% CI: 0.25 to 0.83). Among homosexual men, unemployment was associated with late testing (OR = 2.23, 95% CI: 1.14 to 4.36). The proportion of late testing was still high. Groups classically identified as low risk for HIV infection, particularly heterosexual men in a couple with children, were found to be at high risk for late testing. It seems necessary to improve HIV testing policy in the heterosexual population.

A longitudinal genotypic analysis of the virus found in cellular reservoirs was conducted in 32 patients with undetectable viral loads on highly active antiretroviral therapy (HAART) for investigating whether HIV-1 genetic evolution might lead to changes in virus coreceptor usage during HAART. An R5 to X4 switch in the majority virus population could occur despite of effective HAART, suggesting that potent antiretroviral therapy produces the conditions necessary for the gradual emergence of X4 variants in cellular reservoirs.

Introduction: In the SMART trial, baseline plasma hsCRP, IL6 and D‐dimer levels were strongly correlated to all‐cause mortality. A case‐control study has shown an increase of IL‐6 and D‐dimer levels after one month of antiretroviral therapy (ART) interruption, which was correlated to viral load. Restarting ART was associated to a decrease in D‐dimer but not IL‐6 or hsCRP levels. We assessed biomarkers levels up to 96 weeks in ART‐experienced adults with plasma HIV RNA levels Methods: Stored plasma for 160 participants (80 IT and 80 CT), matched by age, sex and CDC classification, were analyzed blinded for IL‐6, sCD‐14, hsCRP and D‐dimer levels at baseline, week 8 (IT group only), week 16 and week 96. Lower levels of detection for IL‐6, sCD14, hsCRP and D‐Dimer were 1.5 pg/mL, 250 ng/mL, 0.03 µg/mL and 0.21 µg/mL, respectively. The primary objective was to compare changes in IL‐6, hsCRP, sCD14 and D‐dimer plasma levels from baseline to week 8, 16 and 96 in the IT and CT arms. Biomarkers levels were log10 transformed prior to analysis. Results: At baseline, patients were mostly men (86%), with a median age of 40 years, a CD4+ T‐cell count of 768/mm[sup.3], have received a median of 4.7 years of ART and 85% had HIV RNA Compared to baseline, D‐dimer levels significantly increased 8 weeks after ART interruption in the IT arm (+23% fold change, 95% CI +9% to +39%) but reverted to baseline levels at week 16 and remained unchanged at week 96. There was no significant change from baseline in the other biomarker levels in the IT arm. Similarly, no significant change from baseline in biomarker levels was seen in the CT arm up to 96 weeks. Conclusion: Coagulation and inflammatory biomarkers levels remained stable over 96 weeks in well‐suppressed HIV‐infected patient on ART. Following ART interruption there was a significant increase in D‐dimer but not in inflammatory biomarkers levels. This increase was reversed upon reintroduction of ART. These data suggest that ART interruption increases coagulation rather than inflammatory biomarkers., Table 1: Changes in biomarkers levels in participants from the intermittent (IT) vs continuous (CT) treatment arms through 96 weeks (*p=0.002, Wilcoxon test) IL‐6(pg/mL) sCD14(ng/mL) hsCRP(#x00B5;g/mL) D‐dimer(µg/mL) IT CT IT [...]

Abstract Background HIV-1 subtype D infections have been associated with rapid disease progression and phenotypic assays have shown that CXCR4-using viruses are very prevalent. Recent studies indicate that the genotypic algorithms used routinely to assess HIV-1 tropism may lack accuracy for non-B subtypes. Little is known about the genotypic determinants of HIV-1 subtype D tropism. Results We determined the HIV-1 coreceptor usage for 32 patients infected with subtype D by both a recombinant virus phenotypic entry assay and V3-loop sequencing to determine the correlation between them. The sensitivity of the Geno2pheno10 genotypic algorithm was 75% and that of the combined 11/25 and net charge rule was 100% for predicting subtype D CXCR4 usage, but their specificities were poor (54% and 68%). We have identified subtype D determinants in the V3 region associated with CXCR4 use and built a new simple genotypic rule for optimizing the genotypic prediction of HIV-1 subtype D tropism. We validated this algorithm using an independent GenBank data set of 67 subtype D V3 sequences of viruses of known phenotype. The subtype D genotypic algorithm was 68% sensitive and 95% specific for predicting X4 viruses in this data set, approaching the performance of genotypic prediction of HIV-1 subtype B tropism. Conclusion The genotypic determinants of HIV-1 subtype D coreceptor usage are slightly different from those for subtype B viruses. Genotypic predictions based on a subtype D-specific algorithm appear to be preferable for characterizing coreceptor usage in epidemiological and pathophysiological studies.

Background: Human immunodeficiency virus (HIV) infection is associated with a high risk of classical Hodgkin's lymphoma (cHL) in the combined antiretroviral therapy (cART) era. Methods: We analyzed the characteristics and outcome of HIV-associated cHL diagnosed in the modern cART era. The French ANRS-CO16 Lymphovir cohort enrolled 159 HIV-positive patients with lymphoma, including 68 (43%) with cHL. HIV-HL patients were compared with a series of non-HV-infected patients consecutively diagnosed with HL. Results: Most patients (76%) had Ann-Arbor stages III-IV and 96% of patients were treated with ABVD. At diagnosis, median CD4 T-cell count was 387/µL and 94% of patients were treated with cART. All patients received cART after diagnosis. Five patients died from early progression (n = 2), sepsis (1) or after relapse (2). Two additional patients relapsed during follow-up. Two-year overall and progression free survivals (PFS) were 94% [95% CI, 89%, 100%] and 89% [82%, 97%], respectively. The only factor associated with progression or death was age with a relative risk of 8.1 [1.0; 67.0] above 45 years. The PFS of Lymphovir patients appeared similar to PFS of HIVnegative patients, 86% [82%, 90%], but patients with HIV infection displayed higher risk features than HIV-negative patients. Conclusions: Although high-risk features still predominate in HIV-HL, the prognosis of these patients, treated with cART and mainly ABVD, has markedly improved in the modern cART era and is now similar to non-HIV-infected patients. [ABSTRACT FROM AUTHOR]

We present a case wherein striking F-FDG-PET/CT findings initially considered consistent with recurrent disseminated skeletal metastases of breast cancer were later identified as an unusual presentation of disseminated chronic pyogenic osteomyelitis with Staphylococcus aureus and warneri identified on microbiological culture. A 76-year-old female with previous history of breast cancer presented with a 6-month history of pyrexia, myalgia and weight loss. Besides neutrophilia and elevated C-reactive protein, other blood indices, cultures and conventional imaging failed to identify the cause of pyrexia of unknown origin (PUO). F-FDG-PET/CT demonstrated multiple widespread foci of intense FDG uptake in lytic lesions throughout the skeleton. Coupled with previous history of malignancy, findings were strongly suggestive of disseminated metastases of breast cancer. Through targeting an FDG avid lesion, F-FDG-PET/CT aided CT-guided biopsy, which instead identified the lesions as chronic pyogenic osteomyelitis. Following prolonged antibiotic therapy, repeat F-FDG-PET/CT demonstrated significant resolution of lesions. This case demonstrated an unusual presentation of disseminated osteomyelitis on F-FDG-PET/CT and highlighted the use of F-FDG-PET/CT as a trouble shooter in PUO but demonstrated that unusual presentations of benign or malignant pathologies cannot always reliably be differentiated on imaging alone without aid of tissue sampling. Furthermore, this case highlights the potential role F-FDG-PET/CT could provide in assessing response to antibiotic therapy. [ABSTRACT FROM AUTHOR]

Background: HIV-infected patients starting antiretroviral treatment (ART) experience deep and early disorders in fat and bone metabolism, leading to concomitant changes in fat mass and bone mineral density. Methods: We conducted a prospective study in treatment-naive HIV-infected patients randomized to receive two nucleoside reverse transcriptase inhibitors in combination with either a protease inhibitor (PI) or a non-nucleosidic reverse transcriptase inhibitor (NNRTI), to evaluate early changes in body composition, bone mineral density and metabolic markers as differentially induced by antiretroviral therapies. We measured changes in markers of carbohydrate, of fat and bone metabolism, and, using dual-emission X-ray absorptiometry (DXA), body composition and bone mineral density (BMD). Complete data on changes between baseline and after 21 months treatment were available for 35 patients (16 in the PI group and 19 in the NNRTI group). Results: A significant gain in BMI and in total and lower limb fat mass was recorded only in patients receiving PI. A loss of lumbar BMD was observed in both groups, being higher with PI. Plasma markers of bone metabolism (alkaline phosphatase, osteocalcin, collagen crosslaps) and levels of parathormone and of 1,25diOH-vitamin D3 significantly increased in both groups, concomitant with a decline in 25OH-vitamin D3. Lipids and glucose levels increased in both groups but rise in triglyceride was more pronounced with PI. A correlation between loss of BMD and gain of fat mass is observed in patients starting PI. Conclusions: We evidenced an early effect of ART on lipid and bone metabolisms. PI lead to a significant gain in fat mass correlated with a sharp drop in BMD but active bone remodelling is evident with all antiretroviral treatments, associated with low vitamin D levels and hyperparathyroidism. In parallel, signs of metabolic restoration are evident. However, early increases in lean and fat mass, triglycerides, waist circumference and leptin are much more pronounced with PI. [ABSTRACT FROM AUTHOR]

The impact ofminor drug-resistant variants of the type 1 immunodeficiency virus (HIV-1) on the failure of antiretroviral therapy remains unclear. We have evaluated the importance of detecting minor populations of viruses resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTI) during intermittent antiretroviral therapy, a high-risk context for the emergence of drug-resistant HIV-1. We carried out a longitudinal study on plasma samples taken from 21 patients given efavirenz and enrolled in the intermittent arm of the ANRS 106 trial. Allele-specific real-time PCR was used to detect and quantify minor K103N mutants during off-therapy periods. The concordance with ultra-deep pyrosequencing was assessed for 11 patients. The pharmacokinetics of efavirenz was assayed to determine whether its variability could influence the emergence of K103N mutants. Allele-specific real-time PCR detected K103N mutants in 15 of the 19 analyzable patients at the end of an off-therapy period while direct sequencing detected mutants in only 6 patients. The frequency of K103N mutants was ,0.1% in 7 patients by allele-specific real-time PCR without further selection, and .0.1% in 8. It was 0.1%-10% in 6 of these 8 patients. The mutated virus populations of 4 of these 6 patients underwent further selection and treatment failed for 2 of them. The K103N mutant frequency was .10% in the remaining 2, treatment failed for one. The copy numbers of K103N variants quantified by allele-specific real-time PCR and ultra-deep pyrosequencing agreed closely (&rgr; = 0.89 P,0.0001). The half-life of efavirenz was higher (50.5 hours) in the 8 patients in whom K103N emerged (.0.1%) than in the 11 patients in whom it did not (32 hours) (P = 0.04). Thus ultrasensitive methods could prove more useful than direct sequencing for predicting treatment failure in some patients. However the presence of minor NNRTI-resistant viruses need not always result in virological escape. [ABSTRACT FROM AUTHOR]

Background: HIV-1 subtype D infections have been associated with rapid disease progression and phenotypic assays have shown that CXCR4-using viruses are very prevalent. Recent studies indicate that the genotypic algorithms used routinely to assess HIV-1 tropism may lack accuracy for non-B subtypes. Little is known about the genotypic determinants of HIV-1 subtype D tropism. Results: We determined the HIV-1 coreceptor usage for 32 patients infected with subtype D by both a recombinant virus phenotypic entry assay and V3-loop sequencing to determine the correlation between them. The sensitivity of the Geno2pheno10 genotypic algorithm was 75% and that of the combined 11/25 and net charge rule was 100% for predicting subtype D CXCR4 usage, but their specificities were poor (54% and 68%). We have identified subtype D determinants in the V3 region associated with CXCR4 use and built a new simple genotypic rule for optimizing the genotypic prediction of HIV-1 subtype D tropism. We validated this algorithm using an independent GenBank data set of 67 subtype D V3 sequences of viruses of known phenotype. The subtype D genotypic algorithm was 68% sensitive and 95% specific for predicting X4 viruses in this data set, approaching the performance of genotypic prediction of HIV-1 subtype B tropism. Conclusion: The genotypic determinants of HIV-1 subtype D coreceptor usage are slightly different from those for subtype B viruses. Genotypic predictions based on a subtype D-specific algorithm appear to be preferable for characterizing coreceptor usage in epidemiological and pathophysiological studies. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 78-year-old woman who was diagnosed with primary myelofibrosis in June 2011 because of constitutional symptoms including fatigue, itching, and sweats with splenomegaly and cytopenia. The study shows grade 2 fibrosis with JAK2- V617F mutation with the use of bone marrow biopsy. It also shows that the therapeutic effect of ruxolitinib on primary myelofibrosis remained stable although the ruxolitinib plasma concentrations were repeatedly low.

Background: The clinical significance and cellular sources of residual human immunodeficiency virus type 1 (HIV-1) production despite suppressive combination antiretroviral therapy (cART) remain unclear and the effect of low-level viremia on T-cell homeostasis is still debated. Methodology/Principal Findings: We characterized the recently produced residual viruses in the plasma and short-lived blood monocytes of 23 patients with various immunological responses to sustained suppressive cART. We quantified the residual HIV-1 in the plasma below 50 copies/ml, and in the CD14high CD16- and CD16+ monocyte subsets sorted by flow cytometry, and predicted coreceptor usage by genotyping V3 env sequences. We detected residual viremia in the plasma of 8 of 10 patients with poor CD4+ T-cell reconstitution in response to cART and in only 5 of 13 patients with good CD4+ Tcell reconstitution. CXCR4-using viruses were frequent among the recently produced viruses in the plasma and in the main CD14high CD162 monocyte subset. Finally, the residual viremia was correlated with persistent CD4+ and CD8+ T-cell activation in patients with poor immune reconstitution. Conclusions: Low-level viremia could result from the release of archived viruses from cellular reservoirs and/or from ongoing virus replication in some patients. The compartmentalization of the viruses between the plasma and the blood monocytes suggests at least two origins of residual virus production during effective cART. CXCR4-using viruses might be produced preferentially in patients on cART. Our results also suggest that low-level HIV-1 production in some patients may contribute to persistent immune dysfunction despite cART. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is characterized by a tight interplay between Mycobacterium tuberculosis and host cells within granulomas. These cellular aggregates restrict bacterial spreading, but do not kill all the bacilli, which can persist for years. In-depth investigation of M. tuberculosis interactions with granuloma-specific cell populations are needed to gain insight into mycobacterial persistence, and to better understand the physiopathology of the disease. We have analyzed the formation of foamy macrophages (FMs), a granuloma-specific cell population characterized by its high lipid content, and studied their interaction with the tubercle bacillus. Within our in vitro human granuloma model, M. tuberculosis long chain fatty acids, namely oxygenated mycolic acids (MA), triggered the differentiation of human monocyte-derived macrophages into FMs. In these cells, mycobacteria no longer replicated and switched to a dormant non-replicative state. Electron microscopy observation of M. tuberculosis-infected FMs showed that the mycobacteria-containing phagosomes migrate towards host cell lipid bodies (LB), a process which culminates with the engulfment of the bacillus into the lipid droplets and with the accumulation of lipids within the microbe. Altogether, our results suggest that oxygenated mycolic acids from M. tuberculosis play a crucial role in the differentiation of macrophages into FMs. These cells might constitute a reservoir used by the tubercle bacillus for long-term persistence within its human host, and could provide a relevant model for the screening of new antimicrobials against non-replicating persistent mycobacteria. [ABSTRACT FROM AUTHOR]

Reports on the case of a male expatriate with plasmodium falciparum whose neurologic side effects were successfully treated after exposure to two courses of artemether. Clinical manifestations; Result of the neurological examination.